Blood pressure monitoring using a multi-function wrist-worn device

ABSTRACT

The present invention provides non-invasive devices, methods, and systems for determining a pressure of blood within a cardiovascular system of a user, the cardiovascular system including a heart and the user having a wrist covered by skin. More particularly, the present invention discloses a variety of wrist-worn devices having a variety of sensors configured to non-invasively engage the skin on the wrist of the user for sensing a variety of user signals from the cardiovascular system of the user. Generally, approaches disclosed herein may passively track blood pressure values without any interaction required on the part of the user or may allow for on demand or point measurements of blood pressure values by having a user actively interact with the sensors of the wrist-worn device. Approaches disclosed herein further allow for absolute blood pressure values to be determined directly without the requirement for any periodic calibrations or for relative blood pressure values to be tracked so as to provide relative blood pressure indices.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application claims the benefit of U.S. Provisional Appln.No. 62/047,452 filed Sep. 8, 2014; the full disclosure which isincorporated herein by reference in its entirety for all purposes.

The present application is related to U.S. Provisional Appln. Nos.62/047,431 entitled “Systems, Devices, and Methods for Measuring BloodPressure of a User;” 62/047,472 entitled “Wrist Worn Accelerometer ForPulse Transit Time (PTT) Measurements of Blood Pressure;” and 62/047,486entitled “Electrical Coupling of Pulse Transit Time (PTT) MeasurementSystem to Heart for Blood Pressure Measurement;” all of which were filedon Sep. 8, 2014, and are incorporated herein by reference in theirentirety for all purposes.

BACKGROUND OF THE INVENTION

Elevated blood pressure (a.k.a. hypertension) is a major risk factor forcardiovascular disease. As a result, blood pressure measurement is aroutine task in many medical examinations. Timely detection ofhypertension can help inhibit related cardiovascular damage viaaccomplishment of effective efforts in treating and/or controlling thesubject's hypertension.

A person's blood pressure is a continuously changing vital parameter. Asa result, sporadic office blood pressure measurements may beinsufficient to detect some forms of hypertension. For example,hypertension can occur in a pattern that evades detection via isolatedoffice blood pressure measurement. Common hypertension patterns includewhite coat hypertension (elevated only during a limited period of time),borderline hypertension (fluctuating above and below definitional levelsover time), nocturnal hypertension (elevated only during sleeping hoursor not showing the normal drop in pressure during sleep), isolatedsystolic hypertension (elevated systolic pressure with non-elevateddiastolic pressure), and isolated diastolic hypertension (elevateddiastolic pressure with non-elevated systolic pressure). To detect suchhypertension patterns, it may be necessary to perform additional bloodpressure measurements over time to obtain a more complete view of aperson's blood pressure characteristics. Although continuous measurementof blood pressure can be achieved by invasive means, for example, via anintra-arterial pressure sensing catheter, noninvasive blood pressuremeasurement approaches are more typically used.

Current noninvasive blood pressure measurement approaches includeambulatory and home blood pressure measurement strategies. Thesestrategies provide such a more complete view of a person's bloodpressure characteristics and are often employed in recommendedsituations. Ambulatory blood pressure measurement is performed while theperson performs daily life activities. Currently, ambulatory bloodpressure measurements are typically performed every 20 to 30 minutesusing brachial oscillometric blood pressure measurement cuffs.Ambulatory blood pressure measurement may be recommended where there islarge variability in office blood pressure measurements, where a highoffice blood pressure measurement is made in a person with otherwise lowcardiovascular risk, when office and home blood pressure measurementsvary, where resistance to drug treatment of blood pressure is noted orsuspected, where hypotensive episodes are suspected, or wherepre-clampsia is suspected in pregnant women. Home blood pressuremeasurements include isolated self-measurements performed by a person athome. Home blood pressure measurements may be recommended whereinformation is desired regarding the effectiveness of blood pressurelowering medication over one or more dose-to-dose intervals and/or wheredoubt exists as to the reliability of ambulatory blood pressuremeasurement.

Current ambulatory and home blood pressure measurement approaches,however, fail to provide continuous measurement of blood pressure. Thus,convenient and effective approaches for noninvasive continuousmeasurement of blood pressure remain of interest.

BRIEF SUMMARY OF THE INVENTION

The present invention provides non-invasive devices, methods, andsystems for determining a pressure of blood within a cardiovascularsystem of a user, the cardiovascular system including a heart and theuser having a wrist covered by skin. More particularly, the presentinvention discloses a variety of wrist-worn devices having a variety ofsensors configured to non-invasively engage the skin on the wrist of theuser for sensing a variety of user signals from the cardiovascularsystem of the user. Generally, approaches disclosed herein may passivelytrack blood pressure values without any interaction required on the partof the user, which is of particular benefit during overnight monitoringwhen the user is asleep or for other periods of extended monitoring.Passive tracking is particularly ideal as blood pressure values may beobtained consistently, frequently, and/or continuously over a period oftime for potentially longer and more accurate and complete data sets asthis approach is not dependent on user compliance and eliminates anyartifacts (e.g., artificially elevated blood pressure value) associatedwith the act of taking the actual blood pressure measurement (e.g.,white coat syndrome). Alternatively, approaches may allow for on demandor point measurements of blood pressure values by having a user activelyinteract with the sensors of the wrist-worn device to initiate the bloodpressure measurements. For example, the user may engage sensors of thewrist-worn device with another part of their body (e.g., arm, fingers,sternum, ear) or the user may need to engage the arm on which the wristdevice is worn (e.g., volume or pressure oscillometry).

Approaches disclosed herein further allow for absolute blood pressurevalues to be determined directly without the requirement for anyperiodic calibrations (e.g., applanation tonometry as described ingreater detail below) or for relative blood pressure values to betracked so as to provide relative blood pressure indices. The relativeblood pressure values may be calibrated with a reference measurement todetermine blood pressure values on an absolute scale. However, relativeblood pressure values, even if not calibrated to provide absolute bloodpressure values, can be of clinical benefit to the user or the healthcare professional. For example, providing a blood pressure index canshow variations or patterns over time (e.g., trending data) which may beof particular diagnostic or therapeutic value for the user or healthcare professional. Still further, the present invention provideswrist-worn devices that are portable and compact in design and can beeasily and comfortably worn for extended of periods of time. Inparticular, the wrist-worn devices of the present invention provideaccurate and robust blood pressure monitoring and tracking outside theconventional hospital setting, which in turn reduces health care costsand empowers users and their caregivers and/or health care professionalsto make more informed decisions.

Methods utilizing hydrostatic pressure changes to determine a mean orabsolute blood pressure, and more specifically employing modified volumeor pressure oscillometry techniques, are disclosed. In particular, suchmethodologies advantageously utilize the pressure changes associatedwith the natural vertical movement of the user's arm (e.g., activelyraising and lowering their fully extended arm) not as a source of error,but instead to non-invasively measure a mean blood pressure. Methods ofthe present invention for determining a pressure of blood within acardiovascular system of a user may comprise receiving a plurality ofuser signals from the cardiovascular system of the user with a sensor.The sensor non-invasively engages the skin of the user over the wrist ofthe user, each of the user signals being received by the sensor whilethe sensor has an associated height relative to the heart of the user.The user moves the wrist between the signals so that the heights of thesensor differ within a range of heights relative to the heart of theuser. The different heights are maintained for a sufficient length oftime for the device to measure blood pressure at each height. Forexample, the user may slowly raise their arm from a starting positionbelow the heart to and end position above their head or vice versa,wherein the range of heights relative to the heart of the user maycomprises a range from about 1 cm to about 40 cm resulting in ahydrostatic pressure differential in range from just below 1 mmHg toabout 31 mmHg. A signal variation amplitude of the plurality of signalsassociated with the range of heights is identified and a standardpressure of the blood of the user based on the signal variationamplitude and the plurality of signals is determined, the standardpressure having an associated standard blood pressure measurement heightrelative to the heart.

The plurality of user signals may comprise volume or pressure waveformsignals from at least one photoplethysmogram (PPG) or pressure sensor(e.g., pressure sweep for applanation tonometry approaches disclosed ingreater below) respectively non-invasively engaging the skin of the userover the wrist. In this example, the signal variation amplitude may beidentified from a maximum volume or pressure waveform signal based on anoscillation or amplitude of the plurality of volume or pressure waveformsignals of the user. In particular, the volume or pressure waveformsignal associated with the highest oscillation or amplitude comprisesthe maximum volume or pressure waveform signal.

A signal indicative of the height of the sensor relative to the heartassociated with the maximum volume or pressure waveform signal may bereceived and/or calculated from at least a height sensor, accelerometer,and/or a barometric pressure sensor coupled to the wrist-worn device.Still further, user input (e.g., length of arm, height from heart toshoulder, etc.), or other anthropometric data may also be utilized incombination with the height sensor, accelerometer, and/or a barometricpressure sensor signals to determine a height measurement associatedwith the highest oscillation or amplitude. Ideally, the heightmeasurement provides accuracy of ±6 cm for ensuring pressure errors ofless than 3-5 mmHg. The standard or mean arterial pressure may bedetermined based on the maximum volume or pressure waveform signal andthe signal indicative of the height of the sensor relative to the heartassociated with the maximum volume or pressure waveform signal (e.g.,hydrostatic pressure component).

The mean arterial pressure may be generally correlated to thehydrostatic pressure component determined above plus a relativelyconstant, low pressure applied externally to a radial artery beneath theskin of the wrist of the user as the user raises or lowers their armthough the range of heights relative to the heart. This relativelyconstant pressure may be applied over the radial artery by an actuatorcoupled to the wrist-worn device or by user actuation, such as snuglytightening the band of the device around their wrist. This constantpressure range should be within the range of known or expected meanarterial pressure, so that as the local pressure changes with changes inthe arm height, the applied pressure becomes equal to the temporarylocal pressure at some height of the arm relative to the heart. Apressure sensor or an array thereof may be coupled to the wrist-worndevice and non-invasively engaging the skin of the wrist to measure thepressure applied to the wrist as the at least one PPG or pressure sensoris swept through the range of heights relative to the heart of the userfor determining the mean arterial pressure. The mean arterial pressurepoint measurement may further be utilized as a reference blood pressuremeasurement for calibrating relative blood pressure signals, asdescribed in greater detail below. Still further, the determined meanarterial pressure may be transmitted to a second wrist-worn device(e.g., watch), mobile device, tablet, computer, or database for furtherprocessing (e.g., calibration of relative blood pressure signalsabsolute blood pressure tracking), storage (e.g., electronic medicalrecord), retrieval by other devices or programs (e.g., health softwareapplication), and/or display to the user or their health careprofessional.

As described above, relative blood pressure values may be calibratedwith a reference measurement to determine blood pressure values on anabsolute scale. Methods of the present invention for obtaining a bloodpressure measurement of a user comprise sensing, with a first sensor ofa wrist-worn device non-invasively engaging the skin on the wrist of theuser, a first user signal indicative of ventricular ejection of blood(or when a pressure pulse begins propagation) from the heart of theuser, the first sensed ventricular ejection signal having an associatedventricular ejection time. The method may further comprise sensing, witha second sensor of the wrist-worn device non-invasively engaging theskin on the wrist of the user, a second user signal indicative ofarrival of a pressure pulse in the wrist, the second sensed pressurepulse signal associated with the first sensed ventricular ejectionsignal and having an associated pulse arrival time. A relative bloodpressure value may be determined in response to a first pulse transittime (PTT) identified from a difference between the ventricular ejectiontime and the pulse arrival time. An absolute reference blood pressuremeasurement obtained in coordination with the relative blood pressuremay be received from an accurate reference measurement device and theabsolute blood pressure of the relative blood pressure value determinedin response to a difference between the relative blood pressure and theabsolute reference blood pressure.

A plurality of relative blood pressure values determined prior to orsubsequent the first PTT may further be calibrated based on thedifference between the relative blood pressure associated with the firstPTT and the absolute reference blood pressure (e.g., backward orretroactive calibration of existing data or forward calibration of newdata). For example, a second PTT may be determined using the first andsecond sensors of the wrist-worn device, and the absolute blood pressureof the second PTT determined in response to the difference between therelative blood pressure and the absolute reference blood pressure. Inanother example, an absolute blood pressure of a second PTT determinedfrom the first and second sensors of the wrist-worn device and prior tothe first PTT is determined in response to the difference between therelative blood pressure and the absolute reference blood pressure. Itwill be appreciated that the plurality of relative blood pressure valuesmay further be adjusted based on a variety of other factors, such asanthropometric information, vasomotor effects, hydrostatic effects,ambient temperature, user actively level, skin perfusion, skintemperature, or body posture.

Ideally, the plurality of relative blood pressure values are measuredwhen the user is relatively stationary for a short period of time, forexample 30 seconds or less, 20 seconds or less, or 10 seconds or less.Further, in some instances, the plurality of relative blood pressurevalues are preferably measured at a substantially constant sensor heightrelative to the heart of the user to minimize errors due to hydrostaticpressure effects, as discussed in greater below. The absolute referenceblood pressure measurement may be obtained from a variety of sourcesincluding volume oscillometry (as described herein), applanationtonometry devices (as described herein), an oscillometric cuff, or aninput by the user. In some instances, if the difference between thedetermined absolute blood pressure and the reference blood pressure isgreater than ±5 mmHg mean error or ±8 mmHg sigma error, a secondabsolute reference blood pressure measurement may be required foraccurate calibration of the relative pressure values. In this instance,a blood pressure index of the relative blood pressure values may bedisplayed or transmitted instead of the absolute blood pressure values.

Generally, user-dependent calibration of the relative blood pressurevalues may be periodically carried out at least once a week, monthly, oryearly, wherein active measurement approaches may require more frequentrecalibration intervals than passive measurement approaches. Methods ofthe present invention further include recalibration, wherein theabsolute reference blood pressure measurement is obtained at a firsttime period and a second absolute reference blood pressure measurementis obtained in coordination with a second relative blood pressure at asecond time period later than the first time period (e.g., 1 monthlater). An absolute blood pressure of the second relative blood pressurevalue may then be determined in response to a difference between thesecond relative blood pressure and the second absolute reference bloodpressure.

Calibration may be carried out locally by a controller coupled to thewrist-worn device or externally of the wrist-worn device by a mobiledevice, tablet, computer, or database. Further, the plurality ofcalibrated relative blood pressure values may be transmitted to a secondwrist-worn device, mobile device, tablet, computer, or database forfurther processing, storage, retrieval, or display as described herein.The wrist-worn device of the present invention may comprise an activeband, watch, and/or heart rate monitor. For example, the device maycomprise a single integral electronic watch device that includes both aheart rate monitor and blood pressure monitor. Still further, the bloodpressure monitor may be incorporated into a separate active band that isconnectable to the watch device as described in greater detail below.

The first sensor may comprise at least one impedance cardiogram (ICG),electrocardiogram (ECG/EKG), ballistocardiogram (BCG), phonocardiogram(PCG), or seismocardiogram (SCG) sensor coupled to the wrist-worn devicefor sensing the first user signal indicative of ventricular ejection ofblood from the heart of the user. For example, the at least one ICG orECG sensor comprise at least a first pair of dry electrodesnon-invasively engaging glabrous skin on an anterior surface of thewrist of the user and a second pair of dry electrodes contacted by atleast two separate fingers (or a thumb, palm, or wrist) of a handopposite a hand on which the device is worn to provide cross-bodydynamic impedance or electrical potential measurements respectively. Inanother example, the at least one ICG or ECG sensor comprise at least afirst pair of dry electrodes non-invasively engaging glabrous skin on ananterior surface of the wrist of the user and a second pair of dryelectrodes, wherein the second pair of dry electrodes and/or wrist-worndevice non-invasively engage a skin surface of a sternum of the user. Inaddition or alternatively, the least one BCG sensor comprises anaccelerometer non-invasively engaging an anterior surface of the wristso as to passively measure a relative blood pressure. It will beappreciated that engagement with a glabrous skin surface providesimproved electrical contact, but the sensors described herein can alsoengage the posterior surface of the wrist for measurements. Stillfurther, the at least one PCG sensor comprises a sound sensor and thesound sensor, wrist-worn device and/or hand of the wrist-worn devicenon-invasively engage a skin surface of a sternum of the user.Optionally, the at least one SCG sensor comprises an accelerometer andthe accelerometer, wrist-worn device and/or hand of the wrist-worndevice non-invasively engage the sternum.

The second sensor may comprise at least one PPG sensor or pressuresensor coupled to the wrist-worn device for sensing the second usersignal indicative of arrival of the pressure pulse in the wrist. The atleast one PPG sensor may comprise at least one infra-red, red, or greenoptical source and a detector positioned over a radial artery of thewrist (or the finger or arm) of the user. The pressure sensor maycomprise at least one pressure transducer, accelerometer, or straingauge configured to be positioned over a radial artery of the wrist ofthe user.

It will be appreciated that multiple combinations of sensors may beutilized on the wrist-worn device for measuring the first and/or seconduser signals. For example, the first sensor may comprise first andsecond cardiogram sensors coupled to the wrist-worn device for sensingthe first user signal indicative of ventricular ejection of blood fromthe heart of the user, wherein the second cardiogram sensor is differentthan the first cardiogram sensor. In this example, the first cardiogrammay comprise an ICG sensor for a cross body measurement and the secondcardiogram sensor may comprise a BCG sensor for comparison to a passivemeasurement or a SCG/PCG sensor for comparison to an active measurementthat has little or no error due to hydrostatic pressure changes as theSCG/PCG measurement is made at the chest which is relatively alignedwith a height of the heart.

It will be appreciated that multiple combinations of sensors may beutilized on both the wrist-worn device and separate non-wrist worndevices (e.g., mobile device, tablet, stand-alone or attached accessory)for measuring the first and/or second user signals. In another example,an accelerometer of a mobile device may be utilized to provide a SCGmeasurement of the first user signal indicative of ventricular ejectionof blood from the heart of the user by having the mobile device held orstrapped against the chest or placed in the user's shirt pocket whilethe PPG sensor of the wrist-worn device measures the second user signalindicative of arrival of the pressure pulse in the wrist. Still further,non-wrist worn devices may be utilized to provide ECG/ICG measurementsnominally across the heart, a pressure pulse over the radial artery (ora carotid or femoral artery), or a PPG measurement over a finger, thumb,neck, thigh, forehead, or earlobe. For multi-device implementations ofwrist-worn and non-wrist worn devices, time synchronization betweendevices may be carried out via a wireless or telemetry interface (e.g.,Bluetooth or WiFi) or by conducting a signal through the user's body(e.g., small electrical pulse) as a reference strobe.

The present invention further includes a first wrist-worn device fordetermining a pressure of blood within a cardiovascular system of auser. The device may comprise an elongate band non-invasively engagingthe skin on the wrist of the user, wherein the elongate band isreleasably coupleable to a second wrist-worn electronic device. At leastone PTT or pressure sensor may be coupled to the elongate band, thesensor non-invasively engaging the skin over the wrist of the user formeasuring user signals from the cardiovascular system of the user. Acontroller may be coupled to the elongate band and at least one PTT orpressure sensor for determining relative or absolute blood pressuresignals based on the user signals. A power source may be coupled to theelongate band and the controller or the at least one PTT or pressuresensor for providing power to the wrist-worn device. Atelemetry/wireless interface (e.g., Bluetooth or WiFi) may be coupled tothe elongate band and the controller.

The second wrist-worn electronic device may comprise a watch or heartrate monitor having a housing encasing a second controller, second powersource, and second telemetry interface that are distinct and separatefrom the first wrist-worn blood pressure monitoring band.Advantageously, providing bands that are releasably coupleable to thesecond wrist-worn device (e.g., watch) provides for user customizationof the watch based on the desired sensor monitoring. For example, afirst band may comprise an ICG/PPG sensor combination for measuringrelative blood pressure values while a second band may comprise apressure sensor/actuator combination for measuring absolute bloodpressure values. Still further, a third band may monitor an entirelydifferent diagnostic than blood pressure (e.g., heart rate monitor). Theuser may selectively choose between the first, second, or third bandsfor the desired sensor monitoring and may further interchange the bandsat any time period as desired (e.g., a fourth band comprising a passiveBCG/PPG sensor combination for night time blood pressure monitoring anda fifth band comprising an active ECG/PPG sensor combination for daytime blood pressure monitoring) via a releasable coupling feature. Stillfurther, the first wrist-worn device may easily communicate (e.g.,transmit blood pressure values, receive updated instructions, such asnew calibration equations, etc.) with the second wrist-worn device viaWiFi or Bluetooth. The elongate band further comprises at least onereleasable connection or coupling feature for securing the selected bandto the watch or heart rate monitor. For example, the connection orcoupling feature may be mechanical (pin/peg connection, clasp, snap fit,set-screw, or slide-in connector) or magnetic. It will be appreciatedstill further that some embodiments of the present invention may utilizethe same controller, power source, or telemetry interface for both thefirst and second wrist-worn devices. Still further, the first and secondwrist-worn devices (e.g., blood pressure monitor and hear rate monitor)may be incorporated into a single integral electronic watch device.

As described above, the least one PTT sensor may comprise a first andsecond sensors. The first sensor is configured to measure a first usersignal indicative of ventricular ejection of blood from the heart of theuser, the first sensed ventricular ejection signal having an associatedventricular ejection time. The second sensor is configured to measure asecond user signal indicative of arrival of a pressure pulse in thewrist, the second sensed pressure pulse signal associated with the firstsensed ventricular ejection and having an associated pulse arrival time,wherein the relative blood pressure signal is determined from adifference between the ventricular ejection time and the pulse arrivaltime. As described above, the first sensor may comprises at least one(or combination thereof) ICG, ECG, BCG, PCG, and/or SCG sensor coupledto the elongate band. The second sensor may comprise at least one PPGsensor or physical pressure pulse sensor coupled to the elongate band.

Absolute blood pressure bands (e.g., applanation tonometry approaches)may incorporate at least one pressure sensor comprising at least onepressure transducer, piezoelectric film, or piezoresistive filmconfigured to non-invasively engage an anterior surface of the wrist ofthe user and be positioned over a radial artery so as to passively oractively measure the absolute blood pressure signals. The elongate bandmay further comprise at least one actuator configured to apply aconstant or variable pressure over a radial artery of the wrist. Stillfurther, at least one height sensor, barometric pressure sensor,gyroscope, or accelerometer may be coupled to the elongate band so as toaccount for hydrostatic pressure effects.

The telemetry interface of the elongate band may be configured totransmit the relative or absolute blood pressure signals to the secondwrist-worn electronic device, a mobile device, tablet, computer, ordatabase for further processing, storage, retrieval by other devices orprograms, and/or display. For example, the telemetry interface of theelongate band may be configured to transmit the relative or absoluteblood pressure signals to an electronic health or medical record (e.g.,on a database) or health application software (e.g., on a mobile device,tablet, or computer). In another example, the telemetry interface of theelongate band may be configured to transmit the relative or absoluteblood pressure signals to a display on the second wrist-worn electronicdevice or a third non-wrist device (e.g., a mobile device, tablet,computer), the display viewable by the user or a health careprofessional for use in diagnostic or therapeutic decision making. Thetelemetry interface of the elongate band may also be configured totransmit trending data (e.g., blood pressure index) for a time periodbased on the relative blood pressure signals, wherein the time periodcomprises one or more days, weeks, months, or years.

Embodiments of the present invention further include methods forproviding a plurality of active bands for blood pressure monitoring of auser as described above. In one method, a first wrist-worn band isprovided having at least one PIT sensor coupled to the first wrist-wornband and configured to non-invasively engage the skin over the wrist ofthe user for measuring user signals from the cardiovascular system fordetermining relative blood pressure signals. A second wrist-worn band isprovided having at least one pressure sensor coupled to the secondwrist-worn band and configured to non-invasively engage the skin overthe wrist of the user for measuring user signals from the cardiovascularsystem for determining absolute blood pressure signals. The user is ableto selectively choose and/or interchange between the first and secondwrist-worn bands, wherein the selected first or second band isreleasably coupleable to a wrist-worn electronic device. As discussedabove, it will be appreciated that several other combinations of bandshaving various sensing modalities are possible (e.g., first bandrequiring user interaction for blood pressure measurement while thesecond band is passive for blood pressure measurement).

Embodiments of the present invention further include methods forobtaining and transmitting relative blood pressure measurements of auser. One method comprising sensing, with a first sensor of a wrist-worndevice non-invasively engaging the skin on the wrist of the user, firstuser signals indicative of ventricular ejections of blood from the heartof the user, the first sensed ventricular ejection signals each havingan associated ventricular ejection time. A second sensor of thewrist-worn device non-invasively engaging the skin on the wrist of theuser, measures second user signals indicative of pressure pulse arrivalsin the wrist, the second sensed pressure pulse signals associated withthe first sensed ventricular ejection signals, each of the second sensedpressure signals having an associated pulse arrival time. FITmeasurements are identified from a difference between the first sensedventricular ejection signals and the second sensed pressure signals andthe PTT measurements are transmitted directly to a second electronicdevice or database in a non-calibrated (e.g., non-manipulated) format.For example, the second electronic device may comprise a watch, phone,tablet, or a computer. The second electronic device or database may bebetter suited in some instances to store individual calibrationequations and process the PTT measurements to determine absolute bloodpressure values. In some instances, the PTT measurements may betransmitted to a phone or tablet, and then re-transmitted to a clouddatabase for further processing. In other instances, the PTTmeasurements may be transmitted specifically to an electronic health ormedical record or health application software. Still further, trendingdata may be transmitted for a specified time period based on the PTTmeasurements, wherein the time period comprises one or more days, weeks,months, or years. As discussed above, the second electronic device ordatabase may not only process the PTT measurements (e.g., calibration ofrelative blood pressure signals), but also allow for storage of the datain a variety of formats (e.g., non-calibrated PTT measurements, trendingdata, absolute blood pressure values), retrieval of the data by otherdevices or programs, and/or display of the data.

Embodiments of the present invention further include methods forfiltering non-invasive blood pressure measurements from a wrist-worndevice. One method comprises receiving a plurality of relative orabsolute blood pressure signals from at least one pulse transit time(PTT) or pressure sensor coupled to a wrist of a user, filtering therelative or absolute blood pressure signals based on contextualinformation associated with the user, and discarding or masking thefiltered relative or absolute blood pressure signals. Contextualfiltering may be based on a variety of information that may providecontext for any measured blood pressure changes or artifacts. Thecontextual information associated with the user may comprise at leastone of the following: (a) input from the user, (b) health applicationsoftware information associated with the user, (c) an electronic medicalrecord information associated with the user, (d) location informationassociated with the user (e.g., GPS), (e) calendar informationassociated with the user, (f) time information, (g) temperatureinformation, (h) current activity as entered by the user or detected bythe device (e.g. sitting, standing, walking, sleeping, driving), or (i)medication usage/dosage. For example, location information may allowfiltering of blood pressure signals when the user is driving, calendarinformation may allow filtering of blood pressure signals when the useris at an exercise class, and temperature information may allow filteringof blood pressure signals when the user is in an extremely coldenvironment. Filtering relative or absolute blood pressure signals mayalso reduce power consumption of the wrist-worn device as onlynon-filtered relative or absolute blood pressure signals are transmittedto a second wrist worn device, mobile device, tablet, computer, ordatabase. In addition to filtering to remove certain measurements, thecontextual information can also be used to annotate blood pressureinformation over time, in order to discern trends that affect bloodpressure (e.g. blood pressure reduction after walking, blood pressureincrease during driving).

Embodiments of the present invention further include methods foraccounting for hydrostatic effects, particularly for non-invasive bloodpressure measurements from a wrist-worn device having ICG/ECG sensorsfor cross body measurements (e.g., finger to opposite wrist-worn device)or a BCG sensor for passive measurements. For example, pressuredifferentials as large as 30 mmHg can be due to a 40 cm variation in theheight of the sensor relative to the heart during a measurement. Methodsare provided herein for addressing pressure differentials due to takinga measurement when the user's wrist is at a various heights (e.g., downby their side, up in the air, folded across, etc.) relative to theheart. One method comprises receiving relative blood pressure signalsfrom PIT measurements from a wrist-worn device, wherein each PTTmeasurement comprises a time period from ventricular ejection of a heartto pulse arrival at a wrist and the PTT ventricular ejection of theheart is determined from at least one ICG, ECG, or BCG sensor. A signalis received indicative of a height of the sensor relative to the heartassociated with each PTT measurement and the relative blood pressuresignals adjusted based on the height of the sensor relative to the heartsignal associated with each PTT measurement so as to account forhydrostatic pressure differentials. For example, the height signal maybe received and/or calculated from at least a height sensor,accelerometer, gyroscope, and/or a barometric pressure sensor coupled tothe wrist-worn device. Still further, user input or anthropometric datamay also be utilized in combination with the height sensor,accelerometer, gyroscope, and/or a barometric pressure sensor signals todetermine the height measurement. It will be appreciated however thathydrostatic effects may also be negated by taking measurements while theuser is lying down (e.g., BCG passive monitoring while the user isasleep) so that there is little to no variation between the height ofthe wrist sensor relative to the heart or by aligning the wrist sensorrelative to the height of the heart during a measurement (e.g., ICGcontact with the sternum).

The details of one or more implementations are set forth in theaccompanying drawings and the description below. A better understandingof the features and advantages of the present invention will be obtainedby reference to the description and drawings, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a propagation path of a blood pressure pulse fromejection from the left ventricle of the heart to a wrist on which awrist-worn blood pressure measurement device is worn according toembodiments of the present invention.

FIG. 2 illustrates EKG, ICG, and PPG signals relative to a PIT for ablood pressure pulse propagating from the left ventricle to a wrist onwhich a wrist-worn blood pressure measurement device is worn accordingto embodiments of the present invention.

FIG. 3 schematically illustrates a four-electrode configuration used tomeasure impedance of a subject according to embodiments of the presentinvention.

FIGS. 4-5 are schematic side views of wrist-worn blood-pressuremeasurement devices according to embodiments of the present invention

FIG. 6 schematically illustrates electrode locations and related bodyimpedances in an approach for measuring chest-cavity impedancevariations according to embodiments of the present invention.

FIG. 6A is a cross-sectional view of another wrist-worn blood-pressuremeasurement device having exterior electrodes shown engaged with skin ofa user's thorax according to embodiments of the present invention.

FIG. 7 is a schematic diagram of a wrist-worn blood-pressure measurementdevice main unit according to embodiments of the present invention.

FIG. 8 shows typical EKG and ICG data traces according to embodiments ofthe present invention.

FIG. 9 illustrates accelerometer and PPG signals relative to a PTT for ablood pressure pulse propagating from the left ventricle to a wrist onwhich a blood pressure measurement device is worn according toembodiments of the present invention.

FIG. 10 is a schematic side view of a wrist-worn blood pressuremeasurement device held in contact with a user's chest according toembodiments of the present invention.

FIG. 11 is a typical time-domain trace of a measured Seismo-Cardiogramacceleration oriented normal to a user's chest surface according toembodiments of the present invention.

FIG. 12 is a typical frequency-domain Seismo-Cardiogram according toembodiments of the present invention.

FIG. 13 is a typical spectrogram Seismo-Cardiogram according toembodiments of the present invention.

FIG. 14 shows x-axis acceleration, y-axis acceleration, z-axisacceleration, and vector-sum acceleration Seismo-Cardiogram plotsaccording to embodiments of the present invention.

FIG. 15 shows x-axis acceleration, y-axis acceleration, z-axisacceleration, and vector-sum acceleration Ballisto-Cardiogram plotsaccording to embodiments of the present invention.

FIG. 16 is a schematic diagram of a wrist-worn blood-pressuremeasurement device according to embodiments of the present invention.

FIG. 17 is a schematic diagram of an approach for processing recordedacceleration data to identify when blood is ejected from the leftventricle of a user's heart according to embodiments of the presentinvention.

FIG. 18 illustrates a cross-section of tissue layers between a wristskin surface and an underlying artery of a subject.

FIGS. 19-21 illustrate detection of different mean penetration depths oflight emitted by a PPG sensor having returning light detectors disposedat different distances from each of two light sources of the PPG sensoraccording to embodiments of the present invention.

FIGS. 22-23 show relative contribution by subsurface layer to returninglight detected by the light detectors disposed at different distancesfor two different light source wavelengths according to embodiments ofthe present invention.

FIG. 24 illustrates variation of mean penetration depth as a function ofsource-detector separation for two different source light wavelengthsaccording to embodiments of the present invention.

FIG. 25 illustrates variation of the ratio of photons from the deepblood plexus (DBP) layer as a function of source-detector separation fortwo different source light wavelengths according to embodiments of thepresent invention.

FIG. 26 illustrates a propagation path of a blood pressure pulse fromejection from the left ventricle past an auxiliary PPG sensor to a wriston which a wrist-worn blood-pressure measurement device is wornaccording to embodiments of the present invention.

FIG. 27 is a schematic side view of an arm-worn auxiliary PPG sensor fora wrist-worn blood-pressure measurement device according to embodimentsof the present invention.

FIG. 28 is a cross-sectional view of another wrist-worn blood-pressuremeasurement device that can be used with the auxiliary PPG sensor ofFIG. 27 according to embodiments of the present invention.

FIG. 29 illustrates a method for calculating a mean arterial pressure ofa user according to embodiments of the present invention.

FIG. 29A shows a piezoelectric film sensor according to embodiments ofthe present invention.

FIG. 29B shows a piezoelectric pressure sensor according to embodimentsof the present invention.

FIG. 30 illustrates a method for determining a hydrostatic pressureacting on the wrist of a user according to embodiments of the presentinvention.

FIGS. 31A-31C illustrate a method of changing the hydrostatic pressureat the wrist of the user according to embodiments of the presentinvention.

FIGS. 32-35 illustrate various applanation tonometry devices formeasuring pressure pulses at the wrist of the user according toembodiments of the present invention.

FIG. 36 illustrates a fluid bladder according to embodiments of thepresent invention.

FIGS. 37-39 illustrate various pressure sensor arrays that may be usedwith embodiments of the present invention.

FIG. 40 illustrates a method of selectively actuating subsets of theplurality of pressure sensors against a wrist of a user according toembodiments of the present invention.

FIG. 41 illustrates the coupling of a device having a plurality ofsensors and a plurality of actuators to a wrist of a user according toembodiments of the present invention.

FIGS. 42-45 illustrate selective actuation of a skin interface against awrist of a user according to embodiments of the present invention.

FIG. 46A-46C show pressure sensor data obtained from an array ofpressure sensors applied to a user according to embodiments of thepresent invention.

FIG. 47 illustrates a method of calibrating relative blood pressuresignals according to embodiments of the present invention.

FIG. 48 illustrates a schematic diagram of an overall system including awrist-worn band, wrist-worn electronic device, and a mobile phoneaccording to embodiments of the present invention.

FIGS. 49A-49C schematically illustrate a plurality of wrist-worn bandsfor coupling to a wrist-worn electronic device according to embodimentsof the present invention.

FIG. 50 schematically illustrates an active band releasably coupleableto a wrist-worn electronic device according to embodiments of thepresent invention.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 illustrates a propagation path of a blood pressure pulse fromejection from the left ventricle of a subject's heart to a wrist onwhich a wrist-worn blood-pressure measurement device 10 is worn, inaccordance with many embodiments. The wrist-worn device 10 is configuredto detect when the blood corresponding to the blood pressure pulse isejected from the left ventricle of a subjects heart and when the bloodpressure pulse arrives at the wrist-worn device 10. The wrist-worndevice 10 is configured to calculate a pulse transit time (PTT) for theblood pressure pulse for the transit of the blood pressure pulse fromthe left ventricle to the wrist-worn device 10. The determined PTT isthen used to determine one or more blood-pressure values for thesubject.

In general, a PTT is the time it takes for a pulse pressure wave topropagate through a length of a subject's arterial tree. PTT has anonlinear relationship with blood pressure. Factors that can impact howfast a blood pressure pulse will travel at a given blood-pressure in aparticular artery, include, for example, arterial stiffness, arterialwall thickness, and arterial inner diameter. Equation (1) provides afunctional relationship between PTT and mean arterial blood pressure(MAP).

$\begin{matrix}{{MAP} = {\frac{1}{\alpha}{\ln \left\lbrack \frac{\rho \; {D\left( {\Delta \; d} \right)}^{2}}{{{hE}_{0}({PTT})}^{2}} \right\rbrack}}} & (1)\end{matrix}$

where: MAP is mean arterial blood pressure;

-   -   PTT is Pulse Transit Time;    -   h is arterial wall thickness;    -   D is artery diameter;    -   ρ is density of blood;    -   E₀ is the Young's modulus of the artery at zero pressure;    -   α is a subject dependent physiological constant; and    -   Δd is the arterial distance between the subjects left ventricle        and the wrist.

The pressure pulse travels through different arteries during its transitfrom the left ventricle to the wrist. As a result, variation incorresponding variables in equation (1), for example, arterial wallthickness (h), artery diameter (D), and Young's modulus of the artery atzero pressure (E₀), will change the relationship between blood pressureand how fast the blood pressure pulse travels through the respectiveartery. Each blood pressure pulse, however, will travel through the samearteries during transit from the left ventricle to the wrist.Accordingly, a relationship between the overall PTT from the leftventricle to the wrist and MAP can be given by replacing arterial wallthickness (h), artery diameter (D), and Young's modulus of the artery atzero pressure (E₀) with respective effective values suitable for thecombination of all the arteries through which the pressure pulse travelsfrom the left ventricle to the wrist. Therefore, equation (1) can besimplified to the relationship given below in equation (2).

$\begin{matrix}{{MAP} = {\frac{1}{\alpha}{\ln \left\lbrack \frac{K}{({PTT})^{2}} \right\rbrack}}} & (2)\end{matrix}$

where

$K = \frac{\rho \; {D\left( {\Delta \; d} \right)}^{2}}{{hE}_{0}}$

is suitable for the subject and the arterial tree segment over which PITis being measured.

The values of (K) and (α) can be determined using any suitable approach.For example, an oscillometric blood pressure measurement cuff can beused to measure one or more blood pressure values for the subject at orat about the same time as when corresponding one or more PTTs aredetermined for the subject via the wrist-worn device 10. Suitablecalibration data can then be formulated using the oscillometric bloodpressure measurement cuff measured blood pressure values and thecorresponding one or more PTTs for the subject using known approaches.For example, a least squares method can be used to determine suitablevalues or relationships for determining the values of (K) and (α).

A similar approach can be used to predict MAP, systolic blood pressure(SBP), and diastolic blood pressure (DBP) values based on a measured PTTvalue. For example, equations (3), (4), and (5) are example regressionequations that can be used to predict MAP, SBP, and DBP, respectively,from a measured PTT.

MAP=K _(MAP)×[log(PTT)−log(PTT ₀)]+MAP _(BASELINE)  (3)

where: MAP is predicted mean arterial blood pressure;

-   -   MAP_(BASELINE) is a baseline measured MAP;    -   K_(MAP) is a subject dependent constant for MAP;    -   PTT is the measured pulse transit time; and    -   PTT₀ is the measured pulse transit time for MAP_(BASELINE).

SBP=K _(SBP)×[log(PTT)−log(PTT ₀)]+SBP _(BASELINE)  (4)

where: SBP is predicted systolic blood pressure;

-   -   SBP_(BASELINE) is a baseline measured systolic blood pressure;    -   K_(SBP) is a subject dependent constant for systolic blood        pressure;    -   PTT is the measured pulse transit time; and    -   PTT₀ is the measured pulse transit time for SBP_(BASELINE).

DBP=K _(DBP)×[log(PTT)−log(PTT ₀)]+DBP _(BASELINE)  (5)

where: DBP is predicted diastolic blood pressure;

-   -   DBP_(BASELINE) is a baseline measured diastolic blood pressure;    -   K_(DBP) is a subject dependent constant for diastolic blood        pressure;    -   PTT is the measured pulse transit time; and    -   PTT₀ is the measured pulse transit time for DBP_(BASELINE).

FIG. 2 shows an EKG trace segment 12, an ICG trace segment 14, and a PPGsignal 16 relative to a pulse transit time (PTT) 18 for a blood pressurepulse between the left ventricle of the subject to the wrist-worn device10. In many embodiments, the wrist-worn device 10 includes electrodesused to generate an EKG trace and an ICG trace for the subject and a PPGsensor to generate a PPG signal for the subject. The EKG trace segment12 has a segment (QRS) known as the QRS complex, which reflects therapid depolarization of the right and left ventricles. The prominentpeak (R) of the EKG trace corresponds to beginning of contraction of theleft ventricle. A pulse arrival time (PAT) 20 is the time between thepeak (R) of the EKG trace and arrival of the blood pressure pulse at thewrist-worn device 10. As the left ventricle contacts, pressure buildswithin the left ventricle to a point where the pressure exceeds pressurein the aorta thereby causing the aortic valve to open. A pre-ejectionperiod (PEP) 22 is the time period between the peak (R) of the EKG traceand the opening of the aortic valve. The PEP 22 correlates poorly withblood pressure. The ICG trace 14 provides a better indication as to whenthe aortic valve opens. The ejection of blood from the left-ventricleinto the aorta results in a significant temporary decrease in thethoracic impedance of the subject, which corresponds to a temporaryincrease in the ICG trace, which is the negative of the change ofimpedance with time. Accordingly, in many embodiments, the ICG trace 14is processes to identify a start 24 of the temporary increase in the ICGtrace as corresponding to the opening of the aortic valve and the startof the propagation of the blood pressure pulse. In many embodiments, thearrival of the blood pressure pulse is detected via the PPG signal 16,which includes an inflection point 26 that occurs upon arrival of theblood pressure pulse to the wrist-worn device 10.

FIG. 3 schematically illustrates a four-electrode configuration 30 usedto measure impedance of a subject, in accordance with many embodiments.The four-electrode configuration 30 includes a drive current generator32 electrically coupled with a first drive current electrode 34 and asecond drive current electrode 36. In many embodiments, the drivecurrent generator 32 imparts an alternating current to a subject 38 viathe electrodes 34, 36. The four-electrode configuration 30 also includesa voltage sensor 40 electrically coupled with a first sense electrode 42and a second sense electrode 44. The use of the sense electrodes 42, 44,which are separated from the drive current electrodes 34, 36, serves toreduce the impact of impedance and contract resistance by sensingvoltage with electrodes that are transferring much lower levels ofcurrent relative to the current drive electrodes 34, 36. In manyembodiments, the alternating drive current has a frequency between 20kHz and 100 kHz. Drive currents below 20 kHz may create muscleexcitation. And while drive currents at 100 kHz produces skin-electrodeimpedance approximately 100 times lower than at low frequencies, applieddrive currents at greater than 100 kHz may result in stray capacitance.A drive current of about 85 kHz is preferred.

FIG. 4 shows a side view of a wrist-worn blood-pressure measurementdevice 50, in accordance with many embodiments. The wrist-worn device 50includes a main unit 52, a wrist-worn elongate band 54, a first drivecurrent electrode 56, a first sense electrode 58, a second drive currentelectrode 60, a second sense electrode 62, and a PPG sensor 64. Thefirst drive current electrode 56, the first sense electrode 58, and thePPG sensor 64 are: 1) supported on the wrist-worn elongate band 54, 2)positioned and oriented to interface with a subject's wrist upon whichthe wrist-worn device 50 is worn, and 3) operatively connected with themain unit 52. The second drive current electrode 60 and the second senseelectrode 62 are: 1) supported on the wrist-worn elongate band, 2)positioned and oriented to be interfaceable with the subject so that thedrive current travels through the thoracic cavity of the subject (e.g.,with separate fingers on the arm opposite to the arm on which thewrist-worn device 50 is worn), and 3) operatively connected with themain unit 52. The main unit 52 includes circuitry and/or software forimparting drive current through the subject via the first and seconddrive current electrodes 56, 60 and for processing signals from the PPGsensor 64 and the first and second sense electrodes 58, 62 so as tomeasure a PTT and calculate one or more blood pressure values for thesubject based on the PTT.

FIG. 5 shows a side view of another wrist-worn blood-pressuremeasurement device 70, in accordance with many embodiments. Thewrist-worn device 70 includes the same components as for the wrist-worndevice 50, but has the first drive current electrode 56 and the firstsense electrode 58 located to enhance contact pressure with a wrist 72of the subject. In the illustrated embodiment, the first drive currentelectrode 56 is disposed on a directly opposite inside surface of thewrist-worn band 54 relative to the second drive current electrode 60such that contact pressure between, for example, a finger of the subjectand the second drive current electrode 60 transfers compression throughthe wrist-worn band 54 to the first drive current electrode 56, therebyincreasing contact pressure between the first drive current electrode 56and the wrist 72. In a similar fashion, the first sense electrode 58 isdisposed on a directly opposite inside surface of the wrist-worn band 54relative to the second sense electrode 62 such that contact pressurebetween, for example, a finger of the subject and the second senseelectrode 62 transfers compression through the wrist-worn band 54 to thefirst sense electrode 58, thereby increasing contact pressure betweenthe first sense electrode 58 and the wrist 72. Any suitable variationcan be used. For example, the locations of the first drive currentelectrode 56 and the first sense electrode 58 can be exchanged. Asanother example, the electrodes 56, 58, 60, 62 can be located at anyother suitable locations on the wrist-worn band 54. As another example,any suitable number of the electrodes 56, 58, 60, 62 can be disposed onthe main unit 52.

In the illustrated embodiment, the PPG sensor 64 is located on thewrist-worn band 54 so as to be disposed to sense the arrival of theblood-pressure pulse within a radial artery 74 of the subject. Crosssections of the ulna bone 76 and the radius bone 78 of the subject areshown for reference.

FIG. 6 schematically illustrates electrode locations and related bodyimpedances in an approach for measuring chest cavity impedances, inaccordance with many embodiments. In the illustrated approach, the firstdrive current electrode 56 and the first sense electrode 58 are held incontact with the left wrist of the subject. The second drive currentelectrode 60 is contacted by the right index finger of the subject. Thesecond sense electrode 62 is contacted by the right thumb of thesubject. The first and second drive current electrodes 56, 60 impart across-body alternating drive current 80 between the drive currentelectrodes 56, 60. The cross-body drive current 80 propagates throughthe left wrist, through the left arm, through the thoracic cavity,through the right arm, and through the right index finger. The combinedimpedance of the left wrist local to the first drive current electrode56 and the contact impedance of the first drive current electrode 56 andthe left wrist is schematically represented as an impedance (Z1). Thecombined impedance of the right index finger in contact with the seconddrive current electrode 60 and the contact impedance of the second drivecurrent electrode 60 and the right index finger is schematicallyrepresented as an impedance (Z3). The net cross-body impedance betweenthe impedances (Z1 and Z3) is schematically represented as an impedance(Z5). The combined impedance of the left wrist local to the first senseelectrode 58 and the contact impedance of the first sense electrode 58and the left wrist is schematically represented as an impedance (Z2).The combined impedance of the right thumb in contact with the secondsense electrode 62 and the contact impedance of the second senseelectrode 62 and the right thumb is schematically represented as animpedance (Z4). In many embodiments, because the first and second senseelectrodes 58, 62 are configured to measure a voltage difference withouttransferring any significant amount of current, the resulting voltagedrops across the impedances (Z2 and Z4) are small so that the voltagedifference sensed by the first and second sense electrodes 58, 62matches the voltage difference across the impedance (Z5).

FIG. 6A shows a side view of another wrist-worn blood-pressuremeasurement device 71, in accordance with many embodiments. Thewrist-worn device 71 includes the same components as for the wrist-worndevice 70, but has the second drive current electrode 60 and the secondsense electrode 62 located so that they can be engaged with anotherportion of the user via the user positioning the arm on which thewrist-worn device 71 is worn so as to press the electrodes 60, 62 intocontact with any suitable skin portion of the user. For example, FIG. 6Aillustrates the electrodes 60, 62 being pressed against a skin locationon the user's thorax 73 (e.g., lower breast skin opposite to the arm onwhich the device 71 is worn). As another example, the electrodes 60, 62can be pressed against skin on the user's arm opposite to the arm onwhich the device 71 is worn.

FIG. 7 schematically represents an embodiment of a wrist-worn device formeasuring blood pressure. In the illustrated embodiment, the wrist-worndevice includes one or more processors 82, memory 84, a display 86, oneor more input/output devices 88, a data bus 90, an ICG/EKG unit 92, thePPG sensor 64, and a PPG sensor control unit 94. In many embodiments,the memory 84 includes read only memory (ROM) 96, and random accessmemory (RAM) 98. The one or more processors 82 can be implemented in anysuitable form, including one or more field-programmable gate arrays(FPGA).

The ICG/EKG unit 92 includes an ICG/EKG signal processing unit 100, anICG/EKG digital to analog unit 102, an ICG/EKG analog front end unit104, and an ICG/EKG analog to digital unit 106. The signal processingunit 100 generates a digital alternating drive signal (e.g., a digitaldrive signal corresponding to an 85 kHz sinusoidal drive current) andsupplies the digital alternating drive signal to the digital to analogunit 102. The digital to analog unit 102 generates a sinusoidal drivecurrent matching the digital alternating drive signal and supplies thesinusoidal drive current to the analog front end unit 104. The analogfront end 100 supplies the sinusoidal drive current to the first andsecond drive current electrodes 56, 60 for propagation through thesubject (e.g., as the cross-body alternating drive current 80illustrated in FIG. 6). Resulting voltage levels are sensed via thefirst and second sense electrodes 58, 62. Signals from the senseelectrodes 58, 62 are processed by the analog front end 104 to generatean analog voltage signal supplied to the analog to digital unit 106. Theanalog to digital unit 106 converts analog voltage signal to acorresponding digital signal that is supplied to the signal processingunit 100. The signal processing unit 100 then generates correspondingICG/EKG digital data that can be processed by the one or more processors82 to determine the opening of the aortic valve and therefore thecorresponding start of the propagation of a blood pressure pulse fromthe left ventricle to the wrist-worn device.

The PPG sensor unit 64 includes a PPG illumination unit 108 and detectorline array 110. The PPG illumination unit 108 includes two light sources112, 114 which transmit light having different wavelengths onto thewrist. While any suitable wavelengths can be used, the first lightsource 112 generates a beam of light having a wavelength of 525 nm. Thesecond light source 114 generates a beam of light having a wavelength of940 nm. Any suitable number of light sources and correspondingwavelengths can be used and selected to provide desired variation intissue penetrating characteristics of the light. The detector line array110 can include any suitable number of light detectors. In manyembodiments, the light detectors are disposed at a plurality ofdifferent distances from the light sources 112, 114 so that the detectedlight is associated with different mean penetration depths so as toenable detection of the arrival of the blood pressure pulse at differentlayers and/or within a layer of the wrist deeper than a layer sensed bya single light source and single detector PPG sensor. In the illustratedembodiment, the detector line array 110 includes four light detectors116, 118, 120, 122, with each of the light detectors 116, 118, 120, 122being disposed at a different distance from the light sources 112, 114.For example, the light detectors 116, 118, 120, 122 can be disposed at 2mm, 3 mm, 4 mm, 6 mm, or 10 mm respectively, from each of the lightsources 112, 114. Signals generated by the light detectors 116, 118,120, 122 are supplied to the PPG control unit 94, which includes ananalog to digital converter to generate PPG sensor digital data that canbe processed by the one or more processors 82 to determine the arrivalof the blood pressure pulse to the wrist-worn device. The PPG controlunit 94 controls activation of the light sources 112, 114, and canalternately illuminate the light sources 112, 114 at a frequencysufficiently high to enable combined assessment of the PPG sensordigital data generated by illumination of the wrist with the differentwavelengths provided by the light sources 112, 114.

The generated ICG/EKG digital data and the PPG sensor digital data canbe transferred to, and stored in, the RAM 98 for any suitable subsequentuse. For example, the data can be: 1) processed by the one or moreprocessors 82 to determine PTTs and corresponding blood pressure valuesfor the subject, 2) displayed on the display 86, and/or 3) output viathe input/output devices 88 for any suitable purpose such as to a healthcare professional and/or a monitoring service. In many embodiments, theone or more processors 82 processes the ICG/EKG and PPG sensor digitaldata to generate trending data for a time period based on the one ormore relative blood pressure values. Such trending data can be generatedfor any suitable time period, for example, for one or more days, one ormore weeks, one or more months, and/or one or more years. One or moreblood pressure values and/or associated trending data can be: 1) storedin the RAM 98, 2) displayed on the display 86, and/or 3) output via theinput/output devices 88 for any suitable purpose such as to a healthcare professional and/or a monitoring service.

FIG. 8 shows typical EKG and ICG data traces, in accordance with manyembodiments. AC body impedance Z(t) is calculated using the applieddrive current I(t) and the measured resulting voltage difference signalV(t) per equation (6).

Z(t)=V(t)/I(t)  (6)

The ICG signal is then generated by calculating the negative timedifferential of Z(t) as shown in equation (7).

ICG Signal=−dZ/dt  (7)

The EKG signal is generated by voltages generated within the body havingvariations at a much lower frequency (e.g., 0.05-100 Hz) in comparisonto the relatively higher frequency of the impedance drive current (e.g.,85 kHz). Accordingly, signals from the first and second sense electrodes58, 62 can be processed to generate both the ICG and the EKG traces.When both the EKG and the ICG traces are generated, the pre-ejectionperiod (PEP) can be determined. While the PEP time period does notcorrelate well with blood pressure, it may correlate with an extent tovasomotion (vasodilation and vasoconstriction) and thereby serve as anadditional factor that can be used to correlate blood pressure withmeasured PTT. For example, a relationship can be developed wherepredicted blood pressure is a correlated function of both PTT and PEP.

FIG. 9 shows an electrocardiogram (EKG) trace segment 212, aBallisto-Cardiogram (BCG) or Seismo-Cardiogram (SCG) trace segment 214,and a PPG signal 216 relative to a pulse transit time (PTT) 218 for ablood pressure pulse between the left ventricle of the subject to thewrist-worn device 210. In many embodiments, the wrist-worn device 210includes an accelerometer and a PPG or pulse pressure sensor. Theaccelerometer measures one or more accelerations used to generate a BCGand/or a SCG, which can be processed to identify when the blood pressurepulse originates from the subject's left ventricle. A PPG sensor is usedto generate a PPG signal for the subject. The EKG trace segment 212 isshown for reference in describing the operation of the heart. The EKGtrace segment 212 has a segment (QRS) known as the QRS complex, whichreflects the rapid depolarization of the right and left ventricles. Theprominent peak (R) of the EKG trace corresponds to beginning ofcontraction of the left ventricle. A pulse arrival time (PAT) 220 is thetime between the peak (R) of the EKG trace and arrival of the bloodpressure pulse at the wrist-worn device 210. As the left ventriclecontacts, pressure builds within the left ventricle to a point where thepressure exceeds pressure in the aorta thereby causing the aortic valveto open. A pre-ejection period (PEP) 222 is the time period between thepeak (R) of the EKG trace and the opening of the aortic valve. The PEP222 correlates poorly with blood pressure. The BCG/SCG trace 214 can beprocessed to identify when the aortic valve opens. The ejection of bloodfrom the left-ventricle into the aorta results in an associatedacceleration of the chest cavity that is detected via the accelerometerincluded in the wrist-worn device 210. In many embodiments, the arrivalof the blood pressure pulse is detected via the PPG signal 216, whichincludes an inflection point 224 that occurs upon arrival of the bloodpressure pulse to the wrist-worn device 210.

FIG. 10 shows a schematic side view of the wrist-worn device 210 held incontact with a user's chest 225, in accordance with many embodiments.When the wrist-worn device 210 is held in contact with a user's chest,SCG data is generated. When the wrist-worn device 210 is not held incontact with a user's chest, BCG data is generated. The wrist-worndevice 210 includes a main unit 226, a wrist-worn elongate band 228, anaccelerometer 230, and a PPG sensor 232. The accelerometer 230 and thePPG sensor 232 are supported on the wrist-worn elongate band 228 andoperatively connected with the main unit 226. The PPG sensor 232 ispositioned and oriented to interface with a wrist 234 of the user whenthe device 210 is worn on the wrist 234. The main unit 226 includescircuitry and/or software for processing output from the accelerometer230 and the PPG sensor 232 so as to measure a PIT and calculate one ormore blood pressure values for the subject based on the PTT. In theillustrated embodiment, the PPG sensor 232 is located on the wrist-wornband 228 so as to be disposed to sense the arrival of the blood-pressurepulse within a radial artery 236 of the subject. Cross sections of theulna bone 238 and the radius bone 240 of the subject are shown forreference. In described embodiments, the accelerometer 230 is orientedto measure accelerations in each of axes Ax and Ay (in the plane of theuser's chest 225) and axis Az (which is perpendicular to the user'schest 225).

FIG. 11 shows a typical time-domain SCG trace 242 for accelerationmeasured in a direction normal to a user's chest surface, in accordancewith many embodiments. The SCG trace 242 has localized peaks 244, whichcorrespond to the opening of the aortic valve and associated ejection ofblood into the aorta from the user's left ventricle. The SCG trace 242can be processed to identify the localized peaks 244 and the associatedtime points at which the localized peaks occur, thereby identifying oneor more time points for one or more ejections of blood from the leftventricle into the user's aorta. The identified one or more time pointscan be used in conjunction with one or more time points when therespective blood pressure pulses arrive at the wrist as detected by thePPG sensor 232 or alternatively via a pulse pressure sensor to calculatea PTT for the propagation of the blood pressure pulse from the leftventricle to the user's wrist. The calculated PTT can then be used togenerate one or more blood pressure values for the user as describedherein.

FIGS. 12 and 13 show additional plots that can be generated from outputof the accelerometer 230. FIG. 12 shows a typical frequency-domain SCG246 generated from the output of an accelerometer held in contact with auser's chest. The frequency-domain SCG, which can be used to identifyheart rate for the user, which can be used to double check that the timepoints corresponding to the localized peaks 244 are separated by a timeinterval consistent with the identified heart rate. FIG. 13 shows atypical spectrogram SCG, which can also be used to identify heart ratefor the user.

FIG. 14 shows example x-axis acceleration, y-axis acceleration, z-axisacceleration, and vector-sum acceleration SCG plots measured using anaccelerometer held in contact with a subject's chest. Each of the z-axisacceleration (normal to the subject's chest) and the vector-sumacceleration (Atotal) exhibits clear acceleration peaks corresponding torespective ejections of blood from the subject's left ventricle. They-axis acceleration (in plane of the subject's chest) is relatively lessclear with respect to having acceleration peaks corresponding torespective ejections of blood from the subject's left ventricle. And thex-axis acceleration (also in plane with the subject's chest) is theleast clear with respect to having acceleration peaks corresponding torespective ejections of blood from the subject's left ventricle.

FIG. 15 shows example x-axis acceleration, y-axis acceleration, z-axisacceleration, and vector-sum acceleration BCG plots measured using anaccelerometer coupled to a wrist-worn device that is not held in contactwith the subject's chest. These BCG plots show a different order withrespect to which acceleration plots exhibit acceleration peakscorresponding to respective ejections of blood from the subject's leftventricle. Specifically, the y-axis acceleration BCG plot exhibits themost clear acceleration peaks corresponding to respective ejections ofblood from the subject's left ventricle. The vector-sum acceleration(Atotal) BCG plot is the next most clear after the y-axis accelerationBCG plot. Finally, each of the x-axis acceleration and the z-axisacceleration BCG plots appear to be similarly exhibit the least clearacceleration peaks corresponding to respective ejections of blood fromthe subject's left ventricle. As is described herein with reference toFIG. 17, combinations of the component accelerations can be accomplishedso as to exhibit greater signal variability, thereby having cleareracceleration peaks with respect to respective ejections of blood fromthe subject's left ventricle.

FIG. 16 schematically represents an embodiment of the wrist-worn device210. In the illustrated embodiment, the wrist-worn device 210 includesone or more processors 282, memory 284, a display 286, one or moreinput/output devices 288, a data bus 290, the accelerometer 230, the PPGsensor 232, and a PPG sensor control unit 294. In many embodiments, thememory 284 includes read only memory (ROM) 296, and random access memory(RAM) 298. The one or more processors 282 can be implemented in anysuitable form, including one or more field-programmable gate arrays(FPGA) or integrated circuits. The accelerometer 230 can be any suitableaccelerometer (e.g., a three-axis low noise accelerometer).

The PPG sensor unit 232 includes a PPG illumination unit 308 anddetector line array 310. The PPG illumination unit 308 includes twolight sources 312, 314 which transmit light having different wavelengthsonto the wrist. While any suitable wavelengths can be used, the firstlight source 312 generates a beam of light having a wavelength of 525nm. The second light source 314 generates a beam of light having awavelength of 940 nm. Any suitable number of light sources andcorresponding wavelengths can be used and selected to provide desiredvariation in tissue penetrating characteristics of the light. Thedetector line array 310 can include any suitable number of lightdetectors. In many embodiments, the light detectors are disposed at aplurality of different distances from the light sources 312, 314 so thatthe detected light is associated with different mean penetration depthsso as to enable detection of the arrival of the blood pressure pulse atdifferent layers and/or within a layer of the wrist deeper than a layersensed by a single light source and single detector PPG sensor. In theillustrated embodiment, the detector line array 310 includes four lightdetectors 316, 318, 320, 322, with each of the light detectors 316, 318,320, 322 being disposed at a different distance from the light sources312, 314. For example, the light detectors 316, 318, 320, 322 can bedisposed at 2 mm, 3 mm, 4 mm, and 6 mm, respectively, from each of thelight sources 312, 314. Signals generated by the light detectors 316,318, 320, 322 are supplied to the PPG control unit 294, which includesan analog to digital converter to generate PPG sensor digital data thatcan be processed by the one or more processors 282 to determine thearrival of the blood pressure pulse to the wrist-worn device. The PPGcontrol unit 294 controls activation of the light sources 312, 314, andcan alternately illuminate the light sources 312, 314 at a frequencysufficiently high to enable combined assessment of the PPG sensordigital data generated by illumination of the wrist with the differentwavelengths provided by the light sources 312, 314.

Measured acceleration data and the PPG sensor digital data can betransferred to, and stored in, the RAM 298 for any suitable subsequentuse. For example, the data can be: 1) processed by the one or moreprocessors 282 to determine PTTs and corresponding blood pressure valuesfor the subject, 2) displayed on the display 286, and/or 3) output viathe input/output devices 288 for any suitable purpose such as to ahealth care professional and/or a monitoring service. In manyembodiments, the one or more processors 282 processes the accelerationdata and PPG sensor digital data to generate trending data for a timeperiod based on the one or more relative blood pressure values. Suchtrending data can be generated for any suitable time period, forexample, for one or more days, one or more weeks, one or more months,and/or one or more years. One or more blood pressure values and/orassociated trending data can be: 1) stored in the RAM 298, 2) displayedon the display 286, and/or 3) output via the input/output devices 288for any suitable purpose such as to a health care professional and/or amonitoring service.

FIG. 17 illustrates an approach 350 for processing recorded accelerationdata to identify when blood is ejected from the left ventricle of auser's heart, in accordance with many embodiments. In the approach 350,output from the PPG sensor 232 is processed with a suitable bandpassfilter 352 (e.g., a bandpass filter that attenuates frequencies lessthan 0.3 Hz and frequencies greater than 10 Hz) to reduce noise. Thefiltered PPG sensor output is then differentiated with respect to time(act 354) so as to produce a signal that more clearly exhibits when theblood pressure pulse first arrives to the wrist prior to the arrival tothe wrist of a reflection of the blood pressure pulse. In a similarfashion, the output from the accelerometer 230 (three componentacceleration vector data, which varies over time) is also processed witha suitable bandpass filter 356 (e.g., a bandpass filter that attenuatesfrequencies less than 0.3 Hz and frequencies greater than 10 Hz) toreduce noise. The filtered acceleration vector data is then selectivelycombined so that the combined acceleration values exhibit greatervariability with respect to ejections of blood from the subject's leftventricle, thereby exhibiting clearer acceleration peaks correspondingto respective ejections of blood from the subject's left ventricle. Inone variation of the approach 350, a magnitude trace is calculated fromthe three component acceleration vector data (act 358). As illustratedin FIGS. 14 and 15 for each of the vector-sum acceleration data plots(Atotal) for both SCG and BCG, such a magnitude trace can exhibit clearacceleration magnitude peaks corresponding to respective ejections ofblood from the subject's left ventricle. In another variation of theapproach 350, a principal component analysis (PCA) can be performed (act358) to identify a linear combination of the three components of theacceleration data that exhibits maximum acceleration variability,thereby increasing the likelihood that the identified combination willexhibit clear acceleration magnitude peaks corresponding to respectiveejections of blood from the subject's left ventricle while allowing forflexibility in accelerometer orientation on the wrist. The principalcomponent analysis can be accomplished by calculating thethree-dimensional eigenvector associated with the maximum eigenvalue ofthe covariance matrix of the measured acceleration vector samples withina time window. The components of this eigenvector are used as thecoefficients in the linear combination PCA-1 of the accelerationcomponents. The resulting linear combination time samples can then beevaluated to identify peaks corresponding to respective ejections ofblood from the subject's left ventricle. The PCA procedure is repeatedfor subsequent time windows of interest that contain measuredacceleration data. In act 360, identified time points for the arrival ofblood pressure pulses to the wrist are correlated with respective timepoints for the ejection of blood from the user's left ventricle (i.e.,acceleration peaks identified in the combination of the three componentacceleration vector data). For example, each time point for the arrivalof a blood pressure pulse can be correlated with a respective time pointfor the ejection of blood from the left ventricle that falls within apreselected preceding time span (e.g., from 100 ms to 300 ms prior tothe arrival of the blood pressure pulse to the wrist. Any suitablepreceding time span can be used. And the preceding time span used can becustomized to a particular subject to reflect individual variations inpulse wave velocity related characteristics, such as relativedifferences in arterial stiffness.

FIG. 18 illustrates subsurface layers of a subject. The illustratedlayers include: 1) the stratum corneum (about 20 μm thick), 2) theliving epidermis (80 to 100 μm thick), 3) the papillary dermis (150 to200 μm thick), 4) the superficial plexus (80 to 100 μm thick with ablood volume fraction of about 1.10/), 5) the reticular dermis (1400 to1600 μm thick with a blood volume faction of about 0.83%), and 6) thedeep blood net plexus (80 to 120 μm thick with a blood volume fractionof about 4.1%). Upon arrival to the wrist, the blood pressure pulsearrives at the deep blood net plexus layer before propagating to theoverlying layers. As vasomotion (vasodilation and vasoconstriction)plays an important role in regulating blood flow in arterioles andcapillaries further downstream in the arterial tree, using the PPGsensor to detect the arrival of the blood pressure pulse in the deepblood net plexus layer may increase the strength of the correlationbetween blood pressure and PIT by reducing vasomotion inducedvariability of PTT in shallower layers more subject to vasomotioninduced variation in pulse wave velocity of the blood pressure pulse.

FIGS. 19 through 21 illustrate detection of different mean penetrationdepths of light emitted by a PPG sensor having returning light detectorsdisposed at different distances from each of two light sources of thePPG sensor, in accordance with many embodiments. FIG. 19 illustratesdistribution of sensing depths for a combination of a 525 nm lightsource and a point detector disposed 2 mm from the 525 nm light source.FIG. 20 illustrates distributions of sensing depths for the combinationof a 525 nm light source and point detectors disposed at 2 mm, 3 mm, 4mm, and 6 mm from the 525 nm light source, as well as correspondinggraphs of mean penetration depth and ratio of photons from the deepblood net plexus layer to the total detected returned light as afunction of source-detector separation. FIG. 21 illustratesdistributions of sensing depths for the combination of a 940 nm lightsource and point detectors disposed at 2 mm, 3 mm, 4 mm, and 6 mm fromthe 940 nm light source, as well as corresponding graphs of meanpenetration depth and ratio of photons from the deep blood net plexuslayer to the total detected returned light as a function ofsource-detector separation. FIGS. 22 and 23 show contribution of thetotal detected returned light for each layer for each wavelength andsource-detector separation. FIGS. 24 and 25 show combined graphscorresponding to the graphs of FIGS. 20 and 21.

Using the data illustrated in FIGS. 19 through 25, the signals from thedetectors 116, 118, 120, 122, 316, 318, 320, 322 generated for each ofthe light wavelengths generated by the light sources 112, 114, 312, 314can be processed to detect arrival of the blood pressure pulse within aselected layer (e.g., with the deep blood net plexus layer). Forexample, arrival of the blood pressure pulse within the reticular dermislayer can be detected first due to the large percentage of the returninglight incident on the detectors 116, 118, 120, 122, 316, 318, 320, 322that returns from the reticular dermis layer. Once the arrival time tothe reticular dermis layer is determined, the signals during a suitabletime interval prior to the arrival time to the reticular dermis layercan be combined and/or processed to focus attention on detecting theearlier arrival of the blood pressure pulse to the deep blood plexuslayer. Typically, infrared (e.g., 940 nm wavelength) light penetratesdeeper into the skin compared to visible light such as green (e.g., 525nm wavelength) or red (e.g., 660 nm wavelength). Hence, a PPG waveformrecorded from infrared light corresponds to light reflected from deeperblood vessels, while a PPG waveform recorded from green lightcorresponds to light reflected from capillaries near the skin surface.Since the blood pulse arrives at deeper blood vessels earlier thancapillaries near the skin surface, the blood pulse appears in theinfrared PPG before the green PPG at the same location (e.g., on thewrist). A cross correlation of infrared and green PPG signals can beused to determine the relative delay between the arrival of the bloodpulse at deeper blood vessels and the arrival of the blood pulse atcapillaries near the skin surface.

The PPG signal can first be filtered in one of several ways, for examplewith a low-pass filter or with a regression filter. The pulse arrivalcan be detected as the peak of the amplitude of the PPG signal, or the“zero crossing point”. Alternatively, the PPG signal can bedifferentiated with respect to time and the differentiated signal usedto determine a pulse arrival time. This signal processing can beperformed on single pulses, leading to PTTs for each heartbeat. Or, theprocessing can be performed on signals that are an average from morethan one pulse. One multi-beat averaging method is to first transformthe signals (ICG or ECG, and also PPG) into the frequency domain using aFourier Transform. Then a cross-correlation between the two transformedsignals will give a PTT value.

FIG. 26 illustrates another approach for measuring a PTT that can beused to generate one or more blood pressure values for a subject. ThePTT measured in this approach is for the propagation of a blood pressurepulse from an arm-worn auxiliary device 430 to arrival at a wrist-worndevice 432. The auxiliary device 430 and the wrist-worn device 432 canuse any suitable approach for detecting the arrival of theblood-pressure pulse, such as via a PPG sensor as described herein.

FIGS. 27 and 28 show side views of the auxiliary device 430 and thewrist-worn device 432. The auxiliary device 430 includes an arm-wornelongate band 434 and an auxiliary PPG sensor 436 coupled to the band434. The auxiliary device 430 can include one or more reference featuresor marks to as to enable reliable positioning and/or orientation of theauxiliary PPG sensor 436 relative to a selected underlying artery so asto detect arrival of the blood pressure pulse within the selectedunderlying artery. The wrist-worn device 432 can be configured similarto any of the wrist-worn devices described herein with respect to thePPG sensor 464 and can have a main unit 438 that is configured similarto any of the main units described herein with respect to all relevantfunctionality thereof.

FIG. 29 illustrates an exemplary method 510 for calculating a meanarterial pressure with a wrist-worn pressure sensor. At step 510, afterthe wrist-worn device is coupled with a user's wrist, a constantpressure may be applied to the wrist with a pressure sensor coupled witha pressure actuator. Pressure measurements from the wrist may bereceived from the pressure sensor once it is urged against the wrist514. The user may then be instructed to sweep their arm between a firstheight and a second height 516 to vary the hydrostatic pressureexperienced at the wrist. As the user sweeps their arm from the firstheight to the second height, a swept pressure signal may be receivedfrom the pressure sensor where the pressure pulses vary in amplitude dueto the changes in hydrostatic pressure experienced at the wrist as theuser moves their arm. The swept pressure signal may be analyzed toidentify a maximum pressure pulse in the swept pressure signal 520. Ahydrostatic pressure associated with the maximum pressure pulse isobtained 522 after identifying the maximum pressure pulse. A meanarterial pressure may then be calculated 524 based on the obtainedhydrostatic pressure and the constant pressure applied to the wrist. Anindication may then be outputted 526 to provide a user an indication ofthe obtained mean arterial pressure. It will be appreciated however thata PPG sensor of the wrist-worn devices described above may alternativelybe utilized, instead of a pressure sensor, to provide optical volumewaveform signals, wherein a maximum volume waveform signal is identifiedto determine the mean arterial pressure according to FIG. 29.

The exemplary method 510 utilizes the changes in hydrostatic pressurefor applanation of an artery of the user. In many embodiments, themethod 510 may be used for applanation of the radial artery or othersuperficial artery with sufficient bony support of a user. As the wristchanges in height relative to the heart of the user, the amount ofhydrostatic pressure will vary and apply different amounts of pressureat the wrist of the user for applanation of the target artery. Thisexemplary method 510 for calculating mean arterial pressure iscounterintuitive as many prior non-invasive methods of measuring andmonitoring blood pressure teach away from arm movement during bloodpressure monitoring. More specifically, many prior methods require orsuggest that a user maintain their arm in preferred position throughoutthe measurement and/or monitoring of the user's blood pressure. Further,some methods of monitoring or measuring blood pressure may require wristharnesses that lock the user's wrist in a preferred orientation whilethe measurements are taken. A method where the user may obtain bloodpressure measurements and/or monitoring without the need for bulky wristharnesses may provide a more convenient method in which users can easilymeasure their own arterial pressure on the go and outside of a clinicsetting.

In many embodiments, after the user has coupled the device to theirwrist, a constant pressure may be applied 512 by urging a pressuresensor against the wrist of the user. The constant pressure may beapplied by a number of different ways. For example, wrist-worn devicestraps may be manually tightened (e.g., a Velcro strap, adjustablestrap, or the like etc.) or mechanically tightened (e.g., through aratcheting mechanism, or the like, etc.). The straps can be tightenedusing micro-linear actuator, or electroactive polymer (artificialmuscles). In many embodiments a pressure actuator may be used to urgethe pressure sensor against the wrist of the user. For example,solenoids, linear actuators, fluid bladders or the like may be coupledwith a pressure sensor and actuated to urge the pressure sensor againstthe wrist and may also be actuated to reduce an amount of pressureapplied.

In some embodiments, the applied constant pressure could be selected inthe range 80-120 mmHg, which is close to the range of mean arterialpressures of interest. The use of applanation tonometry to determinemean arterial pressure requires that the transmural pressure equalszero, P_transmural=0. The transmural pressure acting across an arterialwall is defined as the difference between the internal pressure andexternal pressure, P_transmural=P_internal−P_external. Under theassumption of negligible resistance from the aorta to large peripheralarteries, the internal pressure P_internal at a peripheral artery is thesum of the central aortic blood pressure and the hydrostatic pressure atthe peripheral artery relative to the aorta. Hence, the internalpressure of a peripheral artery that is below the aorta is greater thanthe blood pressure of the aorta; similarly, the internal pressure of aperipheral artery that is above the aorta is less than the bloodpressure of the aorta. For a constant external pressure, the transmuralpressure is largest when the peripheral artery is at its lowest pointand smallest when the peripheral artery is at its highest point. Whenthe artery is at its lowest point, the transmural pressure is typicallygreater than zero. As the artery is raised from its lowest point, thetransmural pressure decreases until it reaches zero and begins to becomenegative. It follows that for a constant external pressure P_external,the transmural pressure will reach zero at a height that depends on thecentral aortic blood pressure. As the central aortic blood pressureincreases, the transmural pressure equals zero at increasing peripheralartery heights. Conversely, as the central aortic blood pressuredecreases, the transmural pressure equals zero at decreasing peripheralartery heights. For example, a constant pressure may be applied at thewrist such that transmural pressure at the wrist is positive when theuser's arm is at a resting position (e.g., by the user's side whenstanding). The constant pressure may also be configured to allow thetransmural pressure to turn negative after the user raises their arm aheight relative to the user's heart. With such a configuration, anapplanation of a target artery where the arterial wall is flattened andtransmural pressure turns to zero. Here, the arterial pressure isperpendicular to the surface may occur at a height between the restingposition where transmural pressure is positive state and the raisedposition where transmural pressure is negative. At the this height ofthe wrist, the hydrostatic pressure acting on the user's wrist and theconstant pressure applied at the wrist may applanate the artery suchthat the arterial pressure is the only pressure detected by the pressuresensor (e.g., a desired applanation).

Once the pressure sensor is coupled with the wrist of the user, apressure signal/measurement may be received from the pressure sensor514. The received pressure signal may correspond to an arterial pressureof the user. In some embodiments, the pressure sensor may be acapacitive pressure sensor, a piezoelectric film pressure sensor, apiezoresistive microelectromechanical system (MEMS) pressure sensor,bladder fluid or gas pressure sensor, or the like. FIG. 29A shows anexemplary piezoelectric film sensor that may be used with embodiments ofthe present invention described herein. FIG. 29B shows an exemplarypiezoresistive pressure sensor that may be used with embodiments of thepresent invention described herein.

In some embodiments a piezoelectric film pressure sensor may bepreferable as the film may be thin and may better conform to thecontours of the user's wrists. When using a piezoelectric film pressuresensor, some embodiments may actuate the piezoelectric film pressuresensor with a fluid bladder. A fluid bladder pressure sensor identifyingan applied pressure by the fluid bladder may be used to measure staticpressure while the piezoelectric film pressure sensor measures dynamicpressure. The piezoelectric film measures the dynamic pressureoscillations from the artery, while the fluid bladder pressure sensormeasures the static applied pressure from the fluid bladder.

In some embodiments a piezoresistive may be preferable as the film mayalso conform to the contours of the user's wrist and may further measurea static and dynamic pressure.

In many embodiments, an array of pressure sensors may be used to ensurethat at least one of the pressure sensors of the array is positioned ata preferable location relative the target artery of the user. Forexample, in some embodiments, a 12×1 array, two 12×1 arrays, a 3×4array, two 3×4 arrays, or the like of pressure sensors may be appliedtransverse to the radial artery of the wrist. In some embodiments, asingle pressure actuator may be used to urge the entire array of sensorsagainst the target artery. In other embodiments, multiple pressureactuators may be used to urge portions of the array of sensors againstthe target artery. For example, some embodiments of the wrist-worndevice may have each pressure sensor coupled with a pressure actuatorsuch that each individual pressure sensor may be individually urgedagainst and away from the wrist by a desired amount and at differenttimes. Further details of exemplary devices are discussed further below.

The user may be instructed to sweep their arm between a first height anda second height 516. The first height and second heights may be, forexample, a resting position where the user's arm rests against theirside when standing and a raised position where the user's arm is raisedabove their head. In many embodiments, it may be preferable to instructthat the user slowly sweep their hand to different heights so that aplurality of pressure pulses may be measured at different heights.Further, while not essential, it may be preferable to instruct the userto maintain their arm in an extended position or straight orientation(e.g., where the elbow is locked) so that a wrist height measurement,relative to the user's shoulder, may be calculated using an angle of thearm and a shoulder-to-wrist length.

As the user moves their arm to different heights, a swept pressuresignal may be received 518. The swept pressure signal may include aplurality of pressure pulses that vary in amplitude due to changinghydrostatic pressure experienced at the wrist at the different heights.

As discussed above, a desired applanation of a target artery where thearterial wall is flattened and the arterial pressure is perpendicular tothe surface may occur at a desired height between the first wrist height(e.g., resting position where the arm is positioned by the user's side)where the transmural pressure is positive and a second wrist height(e.g., a raised position above the resting position) where thetransmural pressure is negative or vice-versa. At this desired heightwhere the transmural pressure is zero, the hydrostatic pressure actingon the user's wrist and the constant pressure applied at the wrist mayapplanate the artery such that the arterial pressure stress is measuredby the pressure sensor. Accordingly, in a height swept pressure signalwith a plurality of pressure pulses measured at different heights, thedesired applanation of the target artery is associated with the pressurepulse with the largest amplitude (i.e., “maximum pressure pulse”). Thus,after receiving the swept pressure signal 518, a maximum pressure pulsein the swept pressure signal is identified 520 as it is associated withthe desired applanation of the target artery and a corresponding handheight, location, and/or orientation may be recorded for calculating ahydrostatic pressure.

To calculate a mean arterial pressure 524, the applied constant pressureand a hydrostatic pressure acting on the wrist during the measurement ofthe maximum pressure pulse are obtained. The mean arterial pressure(MAP) may be calculated by the following formula:

MAP=P _(applied) −P _(hydrostatic),  (8)

where: P_(applied) is the constant pressure applied at the wrist andP_(hydrostatic) is the hydrostatic pressure acting on the wrist duringthe measurement of the maximum pressure pulse.

P_(hydrostatic) may be calculated by:

P _(hydrostatic) =μgh,  (8a)

where: ρ is the density of blood, g is the gravitational constant, and his the height difference between the heart and the wrist of the user(“heart-to-wrist height”). The average density of blood is approximately1060 kg/m³. The gravitational constant is approximately 9.8 m/s². Theheight difference, h, may be defined as:

h=Height_(heart)−Height_(wrist),  (9)

where h is obtained in centimeters (cm) and where MAP is outputted inmmHg, equation (1) may be rewritten to:

$\begin{matrix}{{{{MAP}({mmHg})} = {{Pressure}_{applied} - {0.78\left( \frac{mmHg}{cm} \right)*{h({cm})}}}},} & (10)\end{matrix}$

Accordingly, MAP may be calculated by obtaining the constant pressureapplied at the wrist and by obtaining the heart-to-wrist height of theuser that is associated with the measurement of the maximum pressurepulse.

FIG. 30 illustrates an exemplary method 528 of calculating thehydrostatic pressure at the wrist 522. At step 530, a signal indicativeof an angle of the pressure sensor may be received while the pressuresensor obtains the swept pressure signal. A shoulder-to-wrist length ofuser may be obtained 532. A height of the sensor relative to the user'sshoulder may be calculated 534 using the signal indicative of the angleof the pressure sensor and the obtained shoulder-to-wrist length. Aheight of the user's shoulder may then be obtained 536 for use incalculating a wrist height 38 based on the shoulder height and thesensor height relative to the shoulder. A user's heart height may thenbe obtained 540. A height difference between the pressure sensor/wristand the heart may then be calculated 542 based on the obtained userheart height 540 and the calculated wrist height 538. Using thecalculated height difference, a hydrostatic pressure acting on the wristat the height of the sensor may be calculated 544 and used to calculatethe MAP 524 (e.g., using equation 10).

In some embodiments, an accelerometer may be coupled with the wrist-worndevice and may output an angle of the pressure sensor 530 whilereceiving the swept pressure signal. The received angle information 530may be used with an obtained shoulder-to-wrist height 532 to identify aheight of the pressure sensor and wrist of the user relative to theshoulder of the user. For example, a shoulder-to-wrist height(Height_(shoulder-to-wrist)) may be calculated with the following:

Height_(shoulder-to-wrist) =l _(shoulder-to-wrist)*sin θ_(wrist);  (11)

where: l_(shoulder-to-wrist) is the length of the shoulder to the wristof the user, and theta is the angle of the wrist/pressure sensorrelative to horizontal identified by the accelerometer.

Optionally, if the accelerometer returned an angle, φ, of the pressuresensor 530 relative to vertical (e.g., where an arm raised straight upreturns an angle of 0° and an arm position straight down returns anangle of 180°), shoulder-to-wrist height may be calculated with thefollowing:

Height_(shoulder-to-wrist) =l _(shoulder-to-wrist)*cos φ_(wrist).  (12)

The length of the shoulder to the wrist of the user may be obtained 532directly from a user input 546 for use in equation (11) or (12). Forexample, a user interface may be provided that requests the user toinput a shoulder-to-wrist length. In response to a user input indicativeof the shoulder-to-wrist length, the device may store the received userinput for use in equation (11) and/or (12).

In some embodiments of the invention, the user may input anthropometricdata 548 and the length of the shoulder to the wrist of the user may beestimated based on the user inputted anthropometric data. For example,in some embodiments, a user may input a gender and a height. In furtherembodiments, other anthropometric data may be obtained such as a user'sage, weight, ethnicity, etc. Based on received anthropometric data,shoulder-to-wrist length may be estimated. For example, in someembodiments, a shoulder-to-wrist length of a male user may be estimatedas approximately 30%-36% of the user's inputted height, and in someembodiments preferably about 330%-34% of the user's inputted height andin further embodiments, even more preferably about 33.4%-33.5% of theuser's inputted height. For some embodiments, a shoulder-to-wrist lengthof a female user may be estimated as approximately 31%-37% of the user'sinputted height, and in some embodiments, even more preferably about33%-35% of the user's inputted height, and in further embodiments, evenmore preferably about 33.3%-34.5% of the user's inputted height.

Thereafter, a user's wrist height (Height_(wrist)) may be calculated 538by obtaining a user shoulder height 536 with the following:

Height_(wrist)=Height_(shoulder)+Height_(shoulder-to-wrist).  (13)

Optionally, equation (13) may be substituted into equation (9) toprovide:

h=Height_(heart-wrist)=Height_(heart)−(Height_(shoulder)+Height_(shoulder-to-wrist)).  (14)

In a similar manner to receiving a shoulder to wrist length, a shoulderheight may be requested and received through a user input 546 or may beestimated using received anthropometric data 548. For example, in someembodiments, a shoulder height of a male user may be estimated asapproximately between 80%-84% of the user's height, and in furtherembodiments, preferably between about 81.5%-82.5% of the user's height,and even more preferably about 81.9%-82% of the users height. For afemale user, a shoulder height may be estimated as approximately between81.5%-83.5% of the user's inputted height, and in further embodiments,preferably between 82%-83% of the user's inputted height, and even morepreferably about 82.4%-82.6% of the user's inputted height.

To calculate for Height_(heart-wrist) using equation (13) or equation(14), a user heart height 540 may be obtained directly through userinput 542 (user inputted and stored for subsequent use) or may beestimated based on anthropometric data inputted by the user 548 (e.g.,gender, height, or the like). In some embodiments, a height of theuser's heart may be estimated as approximately 70-75% of the userinputted height, in further embodiments, preferably about 72%-73% of theuser inputted height and even more preferably about 72.5% of the userinputted height.

Once Height_(heart-wrist) is obtained, a hydrostatic pressure acting onthe wrist may be calculated 544 using equation (8a) and a MAP may becalculated 524 using equation (10).

After calculating an MAP for a user, the method 510 may then proceed tooutput an indication to the user that is indicative of the calculatedMAP 526. The output may comprise the calculated MAP. Alternatively, theoutput may be a general indicator that indicates where the calculatedMAP falls on a spectrum (e.g., good MAP, intermediate MAP, bad MAP). Theoutput may be audio (e.g., a voice or other audio indicator) or visual.For example, the output may be outputted to a display of the device orLEDs may be illuminated to provide the indication. In some embodiments,the output may be communicated to a separate wearable device coupledwith the wrist-worn blood pressure monitoring device. For example, insome embodiments, the wrist-worn blood pressure monitoring device may becoupled with a separate wrist-worn electronics device. The separatedevice may include a separate power source, processor, communicationsport, memory, and inputs/outputs, etc. In further embodiments, theoutput may be transmitted (e.g., wirelessly) to a mobile device of auser. For example, an indication of the calculated MAP may betransmitted to a smartphone, or other portable electronic device (e.g.,tablets, PDAs, laptops, or the like) for recordation, analysis, anddocumentation.

In some embodiments, the wrist-worn blood pressure monitor may output orotherwise transmit received sensor signals (e.g., wrist angle, pressuresignal, swept pressure signal or the like) to a separate device forfurther processing and recordation. This may be advantageous in reducingthe processing power needed in the wrist-worn device, thereby allowingthe device to have a smaller footprint and may allow the device to beoperated for longer periods of time due to a lower power consumption.Further, by transmitting the data to a secondary device (e.g., watch,phone, tablet, or the like) on-board storage and battery requirementsmay be reduced, thereby further allowing the device to have a smallerfootprint.

While generally discussed as instructing the user to actively,intentionally, and/or knowingly carry out the arm sweep for generatingthe swept pressure pulse, other embodiments may be passive where thepressure signals may be received throughout a period of time as the usercarries out daily activities. Other sensor data (e.g., accelerometerdata) may indicate the movement of the sensor to different heights andmay indicate the receipt of a swept pressure signal. The passivelyreceived swept pressure signal (e.g., where the user does not carry outthe arm sweep in response to instructions), may then be analyzed forcalculating a MAP of the user per the methods described above.

Optionally, in some embodiments, an accelerometer and gyroscope on thewrist could be used to trace the trajectory of the wrist during dailymovements and, hence, determine the height between the wrist and theshoulder, the heart-to-wrist height can then be determined by a singlemeasurement of the shoulder-to-heart height.

FIGS. 31A-31C illustrate a user 550 sweeping his arm for producing theswept pressure signal for the exemplary method 510. FIG. 31A illustratesthe user 550 with a wrist-worn device 552 at a first height 554 relativeto his heart 556 where the wrist/wrist-worn device 552 is below theuser's heart 556. FIG. 31B illustrates the user 550 with the wrist-worndevice 552 at an height 558 where the wrist/wrist-worn device 552 isapproximately equal to a height of his heart 556. FIG. 31C illustratesthe user 550 with the wrist-worn device 552 at a second height 560relative to his heart 556 where the wrist/wrist-worn device 552 is abovethe user's heart 556.

In FIG. 31A, Height_(heart-wrist) has a positive value as the heartheight is greater than the wrist height. Accordingly, per equation (8a),the user 550 experiences a positive hydrostatic pressure at the wristwhen the wrist is below the heart 556 of the user. For example, usingequation (8a), the user experiences +40 mmHg of hydrostatic pressure atthe wrist when the wrist is about 51.28 cm below the heart 556. Thus ifthe desired applanation of the target artery (or a measurement of themaximum pressure pulse) occurs when the wrist is below the heart height556, the calculated MAP is less than the applied pressure.

In FIG. 31B, Height_(heart-wrist) is approximately zero. Accordingly,per equation (8a), at this height, no hydrostatic pressure acts on thewrist relative to the heart 556. If the desired applanation of thetarget artery (or a measurement of the maximum pressure pulse) occurswhen the wrist height is equal to the heart height, the calculated MAPis equal to the applied pressure.

In FIG. 31C, Height_(heart-wrist) has a negative value as the heartheight is less than the wrist height, (see equation (9)). Accordingly,per equation (8a), the user 550 experiences a negative hydrostaticpressure at the wrist relative to the heart when the wrist is above theheart 556 of the user 550. For example, using equation (8a), the userexperiences −40 mmHg of hydrostatic pressure at the wrist when the wristis about 51.28 cm above the heart 556. If the desired applanation of thetarget artery (or a measurement of the maximum pressure pulse) occurswhen the wrist is above the heart height 556, the calculated MAP isgreater than the applied pressure.

In many embodiments, the transmural pressure at a low end of the armsweep may be positive where the wrist and device are positioned belowthe heart (e.g., FIG. 31A) and may be negative at a high end of the armsweep where the wrist and device are positioned above the heart (e.g.,FIG. 31C). In such instances, the desired applanation of the targetartery and measurement of the maximum pressure pulse will occur at anintermediate height between the low end of the arm sweep and the highend of the arm sweep where the transmural pressure is zero.

FIG. 32 shows an exemplary device 562 for monitoring and/or measuringblood pressure of a user. The device 562 may include a wrist strap 564and an actuator system 566 supported by the wrist strap 564. Theactuator system 566 may include a tip 567 for coupling with a pressuresensor (not shown) and may be configured to position the pressure sensorat a desired location relative to a coupled wrist.

The wrist strap 564 may be provided for coupling with a wrist of theuser. While illustrated as configured to partially wrap around a user'swrists, other embodiments may fully wrap around a user's wrist. Asdiscussed above, wrist strap 564 may be tightened around the wrist of auser to apply the constant pressure during an MAP measurement. The wriststrap 564 may include clasps, ratcheting mechanisms, or otherengagement/tightening features for coupling and/or tightening the device562 with a wrist of the user.

In some embodiments, the wrist strap 564 may be configured to couplewith/modify a separate wearable device with a strap. For example, thewrist strap 564 may couple to the inner surface/contact surface of astrap of a separate wearable device. In some embodiments, the separatedevice may also be a wrist worn device, such as a watch or the like.

Actuator system 566 may be supported relative to a wrist of the user viawrist strap 564. The actuator system 566 may provide a number of degreesof freedom to a pressure sensor coupled a tip 567 of the actuator system566 relative to the wrist so that a pressure sensor may bepreferentially placed at a desired location on the wrist and with adesired amount of pressure. For example, as illustrated actuator system566 includes a first rail 568 for positioning a coupled pressure sensorperpendicular or transverse to a coupled wrist of a user. Actuatorsystem 566 may further include a second rail 570 for positioning the tip567 along the length of a target artery. Further, actuator system 566may include a linear actuator 572 for urging a pressure sensor coupledthereto against a wrist of a user (e.g., for applying the constantpressure for measuring MAP). In some embodiments, the 2 rail system canbe replaced by an automatic step controlled linear stage positioningsystem. And the linear actuator 572 can be replaced with a voice coilactuator (VCA) or a piezoelectric stack actuator.

The exemplary device 562 may be configured to carry out the exemplarymethod 510. In some embodiments, the exemplary device 562 may be used tomonitor blood pressure using applanation tonometry where the actuator572 is configured to perform a pressure sweep in the Z direction (i.e.into the wrist) for identifying an MAP and then actuated to apply apreferred pressure so that the pressure sensor provides continuous bloodpressure monitoring.

FIG. 33 illustrates another exemplary) device 574 for monitoring and/ormeasuring blood pressure of a user. The device 574 may include a housing576 with a curved configuration with an inner surface 578 configured tomatch the curvature of the underside of the wrist of a user. Housing 576may include slots or engagement features 580 for coupling with a wriststrap (not shown). The housing 576 may include recessed surfaces/slots582 for receiving a sensor array and corresponding recessedsurfaces/slots 584 for receiving sensor leads of a received sensorarray. Further, in some embodiments, housing 576 may include a recessedsurface/slot 586 for receiving a pressure actuator for urging a receivedsensor array against a wrist of a user.

Slots 580 may be configured to receive a wrist strap for coupling thedevice 574 to a wrist of the user. The slot may, for example, receive ahook-and-loop fastener strap (e.g., Velcro® tape, or the like) forsecuring the device 574 to the wrist.

The recessed surface 582 may be configured for receiving a pressuresensor array. In some embodiments the pressure sensor array may comprisecapacitive pressure sensors, piezoresistive MEMS pressure sensors,piezoelectric film pressure sensors, or the like. In some embodiments a12×1 pressure sensor array may be received. The recessed surface 582 mayalign a received sensor array parallel with the wrist strap so that thesensor array traverses the target artery (e.g., radial artery). This mayensure that at least one of the pressure sensors of the pressure sensorarray is positioned over the target artery. In the illustratedembodiment, two recessed surfaces 582 are provided for two 12×1 sensorarrays. While illustrated with two recessed surfaces 582 for receiving12×1 sensor arrays, it should be understood that other embodiments mayinclude single recessed surface 582 or may include three or morerecessed surfaces 582 for receiving sensor arrays. Further, while therecessed surfaces 582 are described as configured to receive 12×1 sensorarrays, it should be understood that embodiments are not limited toreceiving 12×1 sensor arrays. Embodiments may have recessed surfaces toreceive other sensor arrays configurations (e.g., 2×1 sensor arrays, 3×3sensor arrays, 4×4 sensor arrays, 4×3 sensor arrays, 4×6 sensors arraysor the like). Examples of array geometries include, but are not limitedto, rectangular, hexagonal, and arrays with staggered rows or columns.

Recessed surface 586 may be further recessed than recessed surface 582so that the received pressure actuator may urge the received pressuresensors against the wrist of the user. In some embodiments, the recessedsurface 586 may be configured to receive a fluid bladder pressureactuator. The fluid bladder actuator may be configured to be filled withvarious amounts of fluid to urge a received pressure sensor against awrist with vary amounts of pressure. Some embodiments may include afluid bladder pressure sensor for providing a signal indicative of thefluid pressure within the bladder. The recessed surface 586 and thereceived fluid bladder may extend transverse to the recessed surfaces582 so that a single fluid bladder may be actuated to urge a pluralityof received pressure sensor arrays against the wrist of the user with asingle actuation. The bladder actuator in recessed surface 586 may alsobe configured as an array of bladders to actuate the pressure sensor orsensor array.

The device 574 may be configured to carry out the exemplary method 510.In some embodiments, the exemplary device 574 may be used to monitorblood pressure using applanation tonometry where a received pressureactuator in recess 586 is configured to perform a pressure sweep in theZ direction for identifying an MAP and then actuated to apply apreferred pressure so that the pressure sensor(s) provide continuousblood pressure monitoring.

FIG. 34 illustrates another exemplary device 588 for monitoring and/ormeasuring blood pressure of a user. Exemplary device 588 may include anenclosure 590 having slots 592 for receiving a wrist strap for couplingthe device 588 to a wrist of a user. Enclosure 590 may include a slot594 for receiving a pressure bladder or other type of actuator.Enclosure 590 may further house a driver 596 and disposed between thereceived pressure actuator and pressure sensor. The device 588 mayfurther include a pressure sensor (not shown) coupled to a surface ofthe driver 596 that is opposite a surface that couples with the receivedpressure actuator. The pressure sensor or pressure sensor array can beattached to the moving part 596, then be urged against artery.

Similar to the embodiment 574 illustrated in FIG. 33, device 588 mayreceive straps through slots 592 for coupling the device 588 with awrist of the user. Further, the received straps may be used to tightenor to urge the device 588 and a pressure sensor of the device 588against the wrist of the user. The enclosure 590 may position a driver596 between a pressure actuator (e.g., a fluid bladder) and a pressuresensor. The driver 596 may be configured to evenly distribute forcesfrom the pressure actuator across the pressure sensor. This may bepreferred when device 588 couples with a plurality of pressure sensorsand where the pressure actuator comprises a pressure bladder. In someembodiments, a pressure bladder surface may project and retract unevenlyor otherwise have a bulge that applies different amounts of pressuredepending on a contact location along the bladder surface. Thus, with apressure sensor array, some pressure sensors may be applied to a wristwith a different pressure compared to other pressure sensors in thearray. A rigid driver 596 disposed between a fluid bladder and one ormore pressure sensors of device 588 may alleviate these issues by evenlydistributing pressure from the fluid bladder across the pressure sensorarray.

In the illustrated embodiment, the driver 596 may have a cross sectionthat generally resembles a “T,” however other configurations arepossible. The enclosure 590 may include a T opening 598 in a sidewall600 of the enclosure 590. The opening 598 may be dimensioned to receivedriver 596 during assembly of enclosure 590. Once the driver 596 isinserted within the enclosure 590, an insert 602 may be positionedbetween the driver 596 and the opening 598 to secure the driver 596within the enclosure 590.

Device 588 may couple with capacitive, piezoelectric film,piezoresistive pressure sensors or the like for measuring pressure.Further while discussed as using a fluid bladder as a pressure actuator,other actuators may be used (e.g., linear actuators, solenoids or thelike). In some embodiments, utilizing one or more fluid bladders, fluidbladder pressure sensors may be used to provide a signal indicative of afluid pressure with the one or more bladders.

Similar to the embodiments described above, the device 588 may be usedto carry out method 510. Further in some embodiments, the exemplarydevice 588 may be used to monitor blood pressure using applanationtonometry where a received pressure actuator (e.g., fluid bladder) inslot 584 is configured to perform a pressure sweep in the Z direction byurging driver 596 and coupled pressure sensors against the wrist foridentifying an MAP and then actuated to apply a preferred pressure sothat the pressure sensor(s) provide continuous blood pressuremonitoring.

FIG. 35 illustrates yet another exemplary device 604 for measuring ormonitoring blood pressure of a user. The exemplary device 604 includesan elastic housing band 606 configured to couple with a wrist of a user.The elastic housing band 606 may include engagement features 608 forcoupling to a wrist strap. The elastic housing band 606 may furtherdefine a housing for receiving a fluid bladder 610. An inflation port612 may extend from the fluid bladder housing 610 to an outer surface ofthe elastic housing band 606.

Elastic housing band 606 may generally have a curved configuration withan inner surface 614 configured to match the curvature of a user'swrist. The outer surface of the elastic housing band 606 may includeribs 618 and grooves 620 that run transverse to a length of the elastichousing band 606. The ribs 618 and grooves 620 may be configured toprovide additional flexibility in elastic housing band 606, therebyallowing elastic housing band 606 to better conform to the curvature ofa user's wrists.

Fluid bladder housing 610 may be configured to receive a fluid bladder.In many embodiments the device 604 may include an accordion bladder forurging one or more pressure sensors against the wrist of the user. Anaccordion bladder may avoid applying varying pressure along a contactface of the bladder and may thereby provide even distribution ofpressure along a pressure sensor or pressure sensor array.

FIG. 36 illustrates an exemplary accordion bladder 622. Accordionbladder 622 may have side walls 624 that generally define a volume forreceiving fluid for expanding accordion bladder 622 a desired amount.The defined volume may be in fluid communication with inflation port622. The side walls 624 may be generally defined by a plurality ofpleats or bellows that expand and contract with the filling and removalof fluid from the bladder 622. Accordion bladder 622 may further includea generally flat distal face 626 for coupling with a pressure sensor orpressure sensor array. Due to the accordion configuration of the bladder622, fluid filling of the bladder 622 projects the distal face 626 ofthe bladder 622 linearly and evenly, thus increasing surface contactbetween the bladder 622 and a pressure sensor or array of sensors andreducing a bladder intramural stress. In this case the fluid pressureinside the bladder will be evenly exerted on surface 626 and been actingdirectly on the sensor or sensor array, and in turn to the artery.Pressure may then be applied to the pressure sensor/pressure sensorarray and the wrist evenly. Accordingly, in some embodiments, a need fora driver disposed between the pressure actuator and the pressuresensor/pressure sensor array may be avoided by using such a bladder 622.The accordion type bladder can be made of thermoplastics (e.g. nylon,polyethylene, Teflon, etc.).

Device 604 may couple with capacitive, piezoelectric film,piezoresistive MEMS pressure sensors or the like for measuring pressure.Further while discussed as using a fluid bladder as a pressure actuator,other actuators may be used (e.g., linear actuators, solenoids or thelike). In some embodiments, utilizing one or more fluid bladders, fluidbladder pressure sensors may be used to provide a signal indicative of afluid pressure with the one or more bladders and the signal may be usedfor calibrating one or more pressure sensors of the device.

Similar to the embodiments described above, the device 604 may be usedto carry out method 510. Further in some embodiments, the exemplarydevice 604 may be used to monitor blood pressure using applanationtonometry where a received pressure actuator (e.g., accordion fluidbladder) in fluid bladder housing 610 is configured to perform apressure sweep in the Z direction by urging a coupled pressuresensor/pressure sensor array against the wrist for identifying an MAPand then actuated to apply a preferred pressure so that the pressuresensor(s) provide continuous blood pressure monitoring.

FIG. 37 shows an exemplary pressure sensor array 628 that may be usedwith the devices and methods described above. Pressure sensor array 628may be 46 mm×46 mm in dimension and may comprises a plurality ofcapacitive pressure sensors 630 arranged in a 16×16 array. The pressuresensor array 628 may include a cable 632 to couple the pressure sensorarray to a processing device (controller).

Each element may be approximately 2 mm×2 mm in size, thus providing anactive area size of 32 mm×32 mm. The thickness of the active area may beapproximately 1 mm. A scan rate may be up to 39 Hz.

FIG. 38 illustrates another exemplary pressure sensor array 634. Thearray 634 comprises a first array 636 and a second array 638. The firstarray 636 may comprise a 4×3 capacitive pressure sensor array and thesecond array 638 may similarly comprise a 4×3 capacitive pressure sensorarray. Each pressure sensor may be 2×2 mm. Accordingly the array 634 mayhave an active area size of 16 mm×6 mm. The wiring 640 associated withthe first array 636 may be routed to a first side of the pressure sensorarray 634 and the wiring 642 associated with the second array 638 may berouted to a second side of the pressure sensor array 634. Wiring 640,642 may each comprise twelve wires that correspond to each of thepressure sensors in the respective arrays.

The first array 636 and the second array 638 may be symmetric so thatthe application of this sensor array 634 against the user's wrist mayalso symmetric. This type of array 634 may reduce the cantilever beamloading situation (when sensor array with only one side wiring structureis been pressed against artery, the array will undergo a bending modebetween sensor array and wiring pack) and provide a more symmetric loadon the sensor array 634.

The wiring 640, 642 for the sensor array 634 may be backed by a fabricmaterial 644 (e.g., a cloth material). A fabric backing material 644 mayfacilitate installation within a monitoring device and may also reduceundesired bending or stretching loads being applied to the sensor array634.

FIG. 39 illustrates an exemplary pressure actuator-pressure sensorassembly 646 that may be used with the devices and methods disclosedherein. Assembly 646 may include an actuator array 648 coupled with asensor array 650. Each actuator 652 of the actuator array 648 may becoupled to a pressure sensor 654 in the pressure sensor array 650. Eachof the actuators 652 in the pressure actuator array 648 may beindividually controlled to urge each of the pressure sensors 654 of thepressure sensor array 650 against a wrist/target artery of the user bydifferent amounts. For example, different sensors may be urged differentdistances or amounts depending on the curvature, contours, or locationon the wrist where the sensor is to be urged against. Thus someembodiments, may be configured to tailor to different user wrist curvesand contours and may thereby provide more accurate pressuremeasurements. Accordingly, subsets of the pressure sensor array may beurged against different portions of the wrist. Based on pressure sensorreadings, a preferred sensor, sensor location, or sensor signal may beidentified and used for blood pressure measurements and/or monitoring.

In some instances when a constant actuation pressure (e.g., 80 mmHg) isapplied, the sensor array element with the largest static pressure valuemay be different from the element with the largest dynamic pressurevalue. In such instances, the actuator can be moved or a differentactuator can be used at a different position until the same elementexhibits the largest static pressure as well as the largest dynamicpressure when a constant actuation pressure is applied.

While the array of actuators 648 is illustrated as a 5×9 array and thearray of sensors 650 similarly illustrated as a 5×9 array, other arraysizes are possible (e.g., smaller or larger). Further, the actuators 652are illustrated as linear actuators, however other actuators may beused, including but not limited to, fluid bladders, rails actuators,solenoids, or the like. The pressure sensors 654 may be capacitive,piezoresistive, piezoelectric film sensor or the like. The pressuresensor array can be mounted entirely with some backing material to thelinear actuator array, or individual elements may be mounted onindividual actuators to form the entire array.

FIG. 40 illustrates an exemplary method 660 of operating the exemplaryassembly 646 of FIG. 39. At step 662, a first subset of the actuatorsare activated to urge a first subset of the sensors against the wrist.Pressure signals from the first subset of pressure sensors may then bereceived 664. One or more swept pressure signals may be received byvarying an applied pressure with the first subset of actuators 666.Thereafter, a second subset of the actuators may be activated to urge asecond subset of the sensors against the wrist 668. One or more pressuresignals from the second subset of sensors may then be received 670. Oneor more swept pressure signals may be generated by varying the appliedpressure with the second subset of actuators 672. A maximum pressurepulse may then be identified in each of the swept pressure signals 674.A maximum pressure pulse with the largest amplitude out of theidentified maximum pressure pulses may then be identified 676. In someembodiments, the method may include identifying the pressure sensor thatrecorded the maximum pressure pulse with the largest amplitude 678 andidentifying a location of the identified sensor relative to the wrist ofthe user 680. In some embodiments, the identified sensor and theidentified location may be a preferred sensor and location that mostclosely identifies a blood pressure of the user and may be used for MAPmeasurements and blood pressure monitoring via applanation tonometry.

The first/second subset of actuators and the first/second subset ofpressure sensors may be a single actuator and a single pressure sensoror may be more than one actuator and more than one sensor. In someembodiments, the first subset of actuators and sensors may be a firsthalf of an array of actuator-sensor assemblies, while the second subsetof actuators and sensors may be a second half of the array ofactuator-sensor assemblies. In some embodiments, the first subset may bea quarter of an array of actuator-sensor assemblies, and the secondsubset may be another quarter of the array of actuator-sensorassemblies. Where the first subset and the second subset ofactuator-sensor assemblies are less than the total number ofactuator-sensor assemblies of the device, the method 660 may be repeatedfor additional subsets of actuator-sensor assemblies that remain.

While discussed as generating the swept pressure signal by varying thepressure applied by a coupled actuator, a swept pressure signal may, insome embodiments be generated by a change in height of the wristrelative to the heart of the user similar to embodiments describedabove. However, in many embodiments, a passive method (i.e., that doesnot require user arm movement) may be preferable as such methods may beperformed with little to no inconvenience to the user.

Further, in some embodiments, prior to receiving the one or morepressure signals from the second subset of sensors 670, the first subsetof sensors may be retracted away from the wrist.

Additionally, while method 660 is described with steps for processingthe data by identifying a maximum pressure pulse with the largestamplitude out of a plurality of identified maximum pressure pulseswithin each pressure signal, other methods of signal analysis may beprovided.

FIG. 41 illustrates the coupling of a device 682 having a plurality ofsensor-actuator assemblies 684 to a wrist 686 of a user according toembodiments of the present invention. The device 682 may be configuredto measure the blood pressure of a user through applanation of theradial artery 688.

The device 682 includes a strap 690 extends around the wrist 686 andsupports each of the plurality sensor-actuator assemblies 684 againstthe wrist 686. The sensor-actuator assemblies 684 may comprise anactuator 692 coupled with a pressure sensor 694. The plurality ofsensor-actuator assemblies 684 may couple with the wrist 686 at a deviceskin interface 696.

The actuators 692 may be configured to selectively and/or sequentiallyurge regions of the skin interface 696 adjacent the respective actuators692 and disposed between the actuators 692 and the wrist against thewrist 686 of the user. The coupled pressure sensor 694 may measurepressure experienced between the actuators 692 and the wrist 686 andprovide a respective pressure signal to a processor (not shown).Accordingly, the skin interface 696 may comprise a plurality of regionsalong the wrist 686. While illustrated as a cross-section, it should beunderstood that skin interface 696 may comprise an array of regions thatcorrespond to an array of actuators 692.

As illustrated, the skin interface 696 of the device 682 is generallydisposed over the radial artery 688. While the radial artery 688 has asmall footprint, a sensor or sensor array that covers a large region ofthe wrist circumference may ensure that the sensor or at least onesensor of a sensor array is positioned and/or oriented over the radialartery 688 in a desired manner. In some embodiments, given that not allsensors 694 of the device 682 are in a preferred position (e.g., wherethe face of the sensor is perpendicular to a pressure pulse from thetarget artery), it may be preferable to identify a preferred sensor 694and a preferred region for applanation of the radial artery 688. Thismay be carried out by analyzing and comparing the signals from theplurality of sensors 694. For example, the sensors 694 disposed furtherfrom the radial artery 688 may provide weaker pressure signals that arenot as meaningful for determining a blood pressure of a user.

In the illustrated embodiment with a plurality of sensors 694, theactuators 692 may be selectively and/or sequentially activated to urgedifferent regions of the skin interface 696 against the wrist 686 inorder to identify a preferred region for applanation of the radialartery 688. The preferred region for applanation of the radial artery688 may be identified based on pressure signals received from the one ormore sensors 694 of the device 682. For example, the skin interfaceregion disposed between sensor-actuator assembly 698 may be urgedagainst the wrist 686 and a signal may be received from thecorresponding sensor 694 of sensor-actuator assembly 698. Additionally,the skin interface region disposed between the sensor-actuator assembly700 may be urged against the wrist 686 and a signal may be received fromthe corresponding sensor 694 of the sensor-actuator assembly 700. Thesignals from the sensor of assembly 698 and the sensor of assembly 700may then be compared to determine which signal is stronger and/orpreferred. Given that the sensor-actuator assembly 700 is positionedcloser to radial artery 688 and that the surface face of the sensor ofassembly 700 is more perpendicular to pressure pulses from the radialartery 688, the signal from the sensor of assembly 700 may be strongerand preferred in comparison to the signal of the sensor of assembly 698as it is further from the radial artery 688 and oriented at an anglerelative to pressure pulses from the artery 688 and may suffer fromincreased signal loss.

The regions of the skin interface 696 may be selectively urged such thatsubsets of the regions of the skin interface 696 are urged against thewrist 686 at a time. The subsets of regions may be urged by multipleactuators 692 where a subset of the actuators 692 are activated (e.g.,half the actuators, a quarter of the actuators, a single actuator etc.).Accordingly, in some embodiments the subsets of regions may each beurged selectively and sequentially by a single actuator 692 foridentifying a preferred region and sensor 694.

FIG. 42 illustrates the selective actuation of a single region of a skininterface 710 against a wrist of a user according to embodiments of thepresent invention. Device 701 may include pressure sensors 702 that maybe coupled with one of a plurality of actuators 704. The actuators 704may be supported adjacent the wrist by a strap 706. The sensors 702 maycouple with the skin 708 of the user via skin interface 710. Asillustrated in FIG. 42, in some embodiments, a single region of the skininterface 710 disposed between an actuator 704 and the wrist may beurged against the wrist for applanation of the artery 712 using a singleactuator 704. While applanating the artery 712 with the single actuator704, the remaining actuators 704 may not be actively urging respectiveregions of the skin interface 710 against the wrist. This manner ofactuation of regions of the skin interface 710 against the wrist may beperformed selectively and sequentially in order to identify a preferredregion for applanation of the artery 712 and a preferred sensor signalfrom one of the sensors 702.

FIG. 43 illustrates device 701 selectively actuating more than oneregion of a skin interface 710 against a wrist of the user according toembodiments of the present invention. As illustrated in FIG. 43, asubset of regions (e.g., the right half the regions) of the skininterface 710 positioned between actuators 704 and the wrist are urgedagainst a wrist of a user by activating two of the actuators 704 whilethe other two actuators 704 may not be actively urging respectiveregions of the skin interface 710 against the wrist. In someembodiments, pressure signals may only be processed from the advancedpressure sensors 702. In some embodiments, pressure signals may only bereceived from the advanced pressure sensors 702. In some embodiments,the received pressure signals may be processed to identify a bloodpressure of the user or compared to identify a preferred pressure sensor702 between the two advanced pressure sensors 702 and a preferred regionfor applanation. In such a method, processing time may be reduced asonly a subset of pressure signals may be received from the subset urgedregions.

While FIG. 41-FIG. 43 illustrate devices with a plurality of individualsensors 702, other embodiments may utilize a sensor system comprising apressure film sensor. For example, FIG. 44 illustrates a device 800 thatincludes a pressure film sensor 802 that may be coupled with a pluralityof actuators 804. The actuators 804 may be supported adjacent the wristby a strap 806. The sensor 802 may couple with the skin 808 of the uservia skin interface 810. As illustrated in FIG. 44, in some embodiments,a single region of pressure film sensor 802 and a single region of theskin interface 810 may be urged against the wrist for applanation of theartery 812 using a single actuator 804. While applanating the artery 812with the single actuator 804, the remaining actuators 804 may not beactively urging respective regions of the pressure film sensor 802 andthe skin interface 810 against the wrist. This selective actuation ofregions of the pressure film sensor 802 against the wrist may beperformed selectively and sequentially in order to identify a preferredregion of the pressure film sensor 802 and skin interface 810 forapplanation of the artery 812.

FIG. 45 illustrates device 800 selectively actuating a subset of regionsof a skin interface 810 and pressure film sensor 802 against a wrist ofthe user according to embodiments of the present invention. Asillustrated in FIG. 45, a subset of regions (e.g., the right half theregions) of the skin interface 810 are urged against a wrist of a userby activating two of the actuators 804 on the right while the other twoactuators 804 on the left may not be actively urging the respectiveregions of the pressure film sensor 802 against the wrist. Regions ofthe pressure film sensor 802 may be selectively and/or sequentiallyurged against the wrist to identify a preferred region of the skininterface 810 for applanation of the target artery 812 and a preferredregion of the pressure film sensor 802 for receiving pressure signals.

FIG. 46A-46C show sensor data obtained from an array of pressure sensorsapplied to a user according to embodiments of the present invention. Thedata was received from a 1×12 array of pressure sensors applied to asubject's wrist at the radial artery. The pressure actuator was a linearactuator that traveled approximately 6 mm perpendicularly to the wristsurface with a speed of 25 steps/s (each step was approximately 38 μm).The wrist was approximately 15 cm below the heart. The reference bloodpressure taken from an oscillometric brachial monitor was systolic bloodpressure (123 mmHg) and diastolic blood pressure (78 mmHg). Thereference mean arterial pressure was estimated by mean arterialpressure=⅓*(systolic blood pressure)+⅔*(diastolic blood pressure). Thetotal (i.e., AC and baseline) pressure waveform from the sensor elementwith the strongest pulsatile (i.e., AC) component is illustrated in thepressure vs. time chart shown in FIG. 46A. The AC pressure waveformversus time for the same sensor element is illustrated in FIG. 46B. FIG.46C shows the relative AC amplitude vs. baseline from the same sensorelement. Element 20 had the largest pressure amplitude measurementswhile the remaining received relatively weaker pressure signalsAccordingly, element 20 may be a preferred sensor and may be consideredto be placed at a preferred region and/or orientation adjacent thetarget artery. Thus, in some embodiments, a blood pressure measurementmay be calculated based on this pressure signal alone.

FIG. 47 illustrates a method of calibrating relative blood pressuresignals according to embodiments of the present invention. As describedabove, relative blood pressure values may be calibrated with a referencemeasurement to determine blood pressure values on an absolute scale. Atstep 910, a first sensor of a wrist-worn device non-invasively engagingthe skin on the wrist of the user, senses a first user signal indicativeof ventricular ejection of blood from the heart of the user. The firstsensed ventricular ejection signal has an associated ventricularejection time. At step 912, a second sensor of the wrist-worn devicenon-invasively engaging the skin on the wrist of the user, senses asecond user signal indicative of arrival of a pressure pulse in thewrist. The second sensed pressure pulse signal is associated with thefirst sensed ventricular ejection signal and has an associated pulsearrival time. A relative blood pressure value may be then determined inresponse to a first PTT identified from a difference between theventricular ejection time and the pulse arrival time per step 914.

At step 916, an absolute reference blood pressure measurement obtainedin coordination with the relative blood pressure may be received from anaccurate reference measurement device. The absolute reference bloodpressure measurement may be obtained from a variety of sources includingvolume oscillometry (as described herein), an oscillometric cuff, or aninput by the user. In step 918, the absolute blood pressure of therelative blood pressure value may then be determined in response to adifference between the relative blood pressure and the absolutereference blood pressure. The determined absolute blood pressure may becompared to a standard performance threshold (e.g., referencemeasurement) per step 920. For example, if the difference between thethreshold value is greater than ±5 mmHg mean error or ±8 mmHg sigmaerror, a blood pressure index of the relative blood pressure values maybe transmitted instead of the absolute blood pressure values per step926. In addition, a plurality of relative blood pressure valuesdetermined prior to or subsequent the first PTT may further becalibrated based on the difference between the relative blood pressureassociated with the first PTT and the absolute reference blood pressurefor backward or retroactive calibration of existing data or forwardcalibration of new data per step 922.

The blood pressure signals may be filtered based on contextualinformation associated with the user per step 924. As described above,contextual filtering may be based on a variety of information that mayprovide context for any measured blood pressure changes or artifacts.Accordingly, the filtered blood pressure signals may be masked,discarded, or automatically annotated. The plurality of calibratedand/or non-filtered blood pressure values may then be transmitted to asecond electronic device (e.g., watch, mobile device, tablet, orcomputer) or database for further processing (e.g., absolute bloodpressure tracking), storage (e.g., electronic medical record), retrievalby other devices or programs (e.g., health software application), and/ordisplay to the user or their health care professional per step 926. Itwill be appreciated that in some situations, PTT measurements from step914 may be directly filtered per step 924 and/or transmitted per step926 directly to the second electronic device or database in anon-calibrated (e.g., non-manipulated) format. The second electronicdevice or database may be better suited in some instances to storeindividual calibration equations and process the PTT measurements todetermine absolute blood pressure values. As discussed above, the secondelectronic device or database may not only process the PTT measurements(e.g., calibration of relative blood pressure signals), but also allowfor storage of the data in a variety of formats (e.g., non-calibratedPTT measurements, trending data, absolute blood pressure values),retrieval of the data by other devices or programs, and/or display ofthe data.

FIG. 48 illustrates a schematic example of an overall system including afirst wrist-worn band 928, a second wrist-worn electronic device (e.g.,watch 930), and a third non-wrist device (e.g., a mobile device 932)according to embodiments of the present invention. The first wrist-wornband 928 may comprise any one of the blood pressure monitoring sensorarrangements disclosed herein and is configured to non-invasively engagethe skin on the wrist of the user. The elongate band 928 is releasablycoupleable to a second wrist-worn watch 930 as described in greaterdetail below. At least one PTT or pressure sensor 934 may be coupled tothe elongate band 928, the sensor non-invasively engaging the skin overthe wrist of the user for measuring user signals from the cardiovascularsystem of the user. In addition, a height sensor 944 may be coupled tothe elongate band 928 so as to account for any hydrostatic pressureeffects associated with the measured cardiovascular user signals. One ormore processors 936 may be coupled to the elongate band 928 and the atleast one PTT or pressure sensor 934 for determining relative orabsolute blood pressure signals based on the user signals. The one ormore processors 936 can be implemented in any suitable form, includingone or more field-programmable gate arrays (FPGA). The elongate band 928may further include memory 938, such as read only memory (ROM) and/orrandom access memory (RAM). A power source 940 may also be coupled tothe elongate band 928 and the processor 936 or the at least one PTT orpressure sensor 934 for providing power to the wrist-worn band 928. Atelemetry/wireless interface 942 (e.g., Bluetooth or WiFi) may also becoupled to the elongate band 928 and the processor 936.

The second wrist-worn watch 930 may comprise one or more heart ratemonitor sensor(s) 946, a second processor 948, a second power source950, a second memory 952, a second telemetry interface 954, and/or auser display 956 that are enclosed within a distinct and separatehousing from the first wrist-worn blood pressure monitoring band 928.The first wrist-worn band 928 may easily communicate (e.g., transmitblood pressure values, receive updated instructions, such as newcalibration equations, etc.) with the second wrist-worn watch 930 viaWiFi or Bluetooth. Still further, the telemetry interface 942 of theelongate band 928 may be configured to communicate not only with thesecond wrist-worn watch 930, but also with the third non-wrist device(mobile device 932). For example, the telemetry interface 942 of theelongate band 928 may be configured to transmit the relative or absoluteblood pressure signals to a health application software 958 on themobile device 932. The mobile device 932 may in turn display therelative blood pressure signals 960 and/or the absolute blood pressuresignals 962 in a graphical format dictated by the health applicationsoftware 958 for a time period of a day, week, month, or year. The bloodpressure graphs 960, 962 may then be viewable by the user or a healthcare professional for use in diagnostic or therapeutic decision making.Still further, the mobile device 932 may be configured to receive theblood pressure signals from the wrist-worn band 928 and/or wrist-wornwatch 930 and in turn re-transmit this data to a cloud database 964 forfurther processing, storage, or retrieval by other devices or programs.For example, the blood pressure measurements may be transmittedspecifically to an electronic health or medical record database 966.

Referring now to FIGS. 49A-49C, providing bands 928 that are releasablycoupleable to the watch 930 provides for user customization of the watch930 based on the desired sensor monitoring (e.g., absolute, relative,passive, active, etc.). For example, a first applanation tonometry band968 as illustrated in FIG. 49A may comprise a plurality of pressuresensors 970 and actuators 972 for measuring absolute blood pressurevalues. The pressure sensors 970 may comprise pressure transducers asillustrated or still further a piezoelectric film or piezoresistive filmfor sensing. The pressure sensors 970 are configured to non-invasivelyengage an anterior surface of the wrist of the user and be positionedover a radial artery so as to passively or actively measure the absoluteblood pressure signals. The actuators 972 urge each of the pressuresensors 970 against the wrist of the user by applying a constant orvariable pressure thereto.

FIGS. 49B and 49C illustrate bands 974, 982 for measuring relative bloodpressure values. As described above, the least one PTT sensor maycomprise first and second sensors. The first sensor is configured tomeasure a first user signal indicative of ventricular ejection of bloodfrom the heart of the user, the first sensed ventricular ejection signalhaving an associated ventricular ejection time. The second sensor isconfigured to measure a second user signal indicative of arrival of apressure pulse in the wrist, the second sensed pressure pulse signalassociated with the first sensed ventricular ejection and having anassociated pulse arrival time, wherein the relative blood pressuresignal is determined from a difference between the ventricular ejectiontime and the pulse arrival time. The first sensor may comprises at leastone (or combination thereof) ICG, ECG, BCG, PCG, and/or SCG sensorcoupled to the elongate band. The second sensor may comprise at leastone PPG sensor or physical pressure pulse sensor coupled to the elongateband.

With reference to FIG. 49B, a second band 974 may comprise an ICG/PPGsensor arrangement for measuring relative blood pressure values. Inparticular, the at least one ICG sensor may comprise at least a firstpair of dry electrodes 976 non-invasively engaging glabrous skin on ananterior surface of the wrist of the user and a second pair of dryelectrodes 978 contacted by at least two separate fingers (or a thumb,palm, or wrist) of a hand opposite a hand on which the device is worn toprovide cross-body dynamic impedance measurements. The PPG sensor 980may comprise at least one infra-red, red, or green optical source and adetector positioned over a radial artery of the wrist (or the finger orarm) of the user. With reference to FIG. 49C, a third band 982 maycomprise a BCG/PPG sensor arrangement for passive monitoring of relativeblood pressure values. The BCG sensor 984 may comprise an accelerometernon-invasively engaging an anterior surface of the wrist so as topassively measure a relative blood pressure. At least one height sensor996 may be coupled to the elongate band 982 so as to account forhydrostatic pressure effects. The user may selectively choose betweenthe first 968, second 974, or third bands 982 for the desired sensormonitoring and may further interchange the bands at any time period asdesired via a releasable coupling feature 994. The at least onereleasable connection or coupling feature 994 of the elongate bands 968,974, or 982 may help secure the selected band 986 to the heart ratemonitor watch device 930.

As shown in FIG. 50, a fourth selected band 986 is releasably coupleableto the watch device 930 and includes two types of sensor monitoringarrangements. An ECG sensor arrangement is provided for cross-bodyelectrical potential measurements and a SCG sensor arrangement forcomparison of the ECG measurement to another active measurement that haslittle or no error due to hydrostatic pressure changes as the SCGmeasurement is made at the chest which is relatively aligned with aheight of the heart. The ECG sensor comprises a first pair of dryelectrodes 988 non-invasively engaging glabrous skin on an anteriorsurface of the wrist of the user and a second pair of dry electrodes 990contacted by at least two separate fingers (or a thumb, palm, or wrist)of a hand opposite a hand on which the device is worn. The SCG sensor992 comprises an accelerometer and the accelerometer 992, wrist-wornband 986 and/or hand of the wrist-worn device non-invasively engage thesternum.

It will be appreciated that personal information data may be utilized ina number of ways to provide benefits to a user of a device. For example,personal information such as health or biometric data may be utilizedfor convenient authentication and/or access to the device without theneed of a user having to enter a password. Still further, collection ofuser health or biometric data (e.g., blood pressure measurements) may beused to provide feedback about the user's health and/or fitness levels.It will further be appreciated that entities responsible for collecting,analyzing, storing, transferring, disclosing, and/or otherwise utilizingpersonal information data are in compliance with established privacy andsecurity policies and/or practices that meet or exceed industry and/orgovernment standards, such as data encryption. For example, personalinformation data should be collected only after receiving user informedconsent and for legitimate and reasonable uses of the entity and notshared or sold outside those legitimate and reasonable uses. Stillfurther, such entities would take the necessary measures forsafeguarding and securing access to collected personal information dataand for ensuring that those with access to personal information dataadhere to established privacy and security policies and/or practices. Inaddition, such entities may be audited by a third party to certifyadherence to established privacy and security policies and/or practices.It is also contemplated that a user may selectively prevent or block theuse of or access to personal information data. Hardware and/or softwareelements or features may be configured to block use or access. Forinstance, a user may select to remove, disable, or restrict access tocertain health related applications that collect personal information,such as health or fitness data. Alternatively, a user may optionallybypass biometric authentication methods by providing other secureinformation such as passwords, personal identification numbers, touchgestures, or other authentication methods known to those skilled in theart.

In the foregoing specification, the invention is described withreference to specific embodiments thereof, but those skilled in the artwill recognize that the invention is not limited thereto. Variousfeatures and aspects of the above-described invention can be usedindividually or jointly. Further, the invention can be utilized in anynumber of environments and applications beyond those described hereinwithout departing from the broader spirit and scope of thespecification. The specification and drawings are, accordingly, to beregarded as illustrative rather than restrictive. It will be recognizedthat the terms “comprising,” “including,” and “having,” as used herein,are specifically intended to be read as open-ended terms of art.

While the exemplary embodiments have been described in some detail, byway of example and for clarity of understanding, those of skill in theart will recognize that a variety of modifications, adaptations, andchanges may be employed.

1. A method for determining a pressure of blood within a cardiovascularsystem of a user, the cardiovascular system including a heart and theuser having a wrist covered by skin, the method comprising: receiving aplurality of user signals from the cardiovascular system of the userwith a sensor, the sensor non-invasively engaging the skin of the userover the wrist of the user, each of the user signals being received bythe sensor while the sensor has an associated height relative to theheart of the user, wherein the user moves the wrist between the signalsso that the heights of the sensor differ within a range of heightsrelative to the heart of the user; identifying a signal variationamplitude of the plurality of signals associated with the range ofheights; and determining a standard pressure of the blood of the userbased on the signal variation amplitude and the plurality of signals,the standard pressure having an associated standard blood pressuremeasurement height relative to the heart.
 2. The method of claim 1,wherein the plurality of user signals comprises volume or pressurewaveform signals from at least one photoplethysmogram (PPG) or pressuresensor respectively non-invasively engaging the skin of the user overthe wrist.
 3. The method of claim 2, wherein identifying the signalvariation amplitude further comprises identifying a maximum volume orpressure waveform signal based on an oscillation or amplitude of theplurality of volume or pressure waveform signals of the user.
 4. Themethod of claim 3, wherein a volume or pressure waveform signalassociated with the highest oscillation or amplitude comprises themaximum volume or pressure waveform signal.
 5. The method of claim 3,further comprising receiving a signal indicative of the height of thesensor relative to the heart associated with the maximum volume orpressure waveform signal.
 6. The method of claim 5, wherein receiving asignal indicative of the height of the sensor relative to the heartfurther comprises calculating a height measurement from at least aheight sensor, accelerometer, gyroscope, user input, anthropometricdata, or a barometric pressure sensor.
 7. The method of claim 5, whereindetermining the standard pressure of the blood of the user comprisesdetermining a mean arterial pressure based on the maximum volume orpressure waveform signal and the signal indicative of the height of thesensor relative to the heart associated with the maximum volume orpressure waveform signal.
 8. The method of claim 7, further comprisingreceiving a pressure measurement applied to a radial artery beneath theskin of the wrist of the user for determining the mean arterialpressure, wherein a relatively constant pressure is applied over theradial artery as the at least one PPG or pressure sensor is sweptthrough the range of heights relative to the heart of the user.
 9. Themethod of claim 7, further comprising calibrating non-invasive relativeblood pressure signals based on the determined mean arterial pressure ofthe user.
 10. The method of claim 1, wherein the range of heightsrelative to the heart of the user comprises a range from about 1 cm toabout 40 cm.
 11. The method of claim 1, further comprising transmittingthe determined mean arterial pressure to a second wrist-worn device,mobile device, tablet, computer, or database. 12.-33. (canceled)
 34. Afirst wrist-worn device for determining a pressure of blood within acardiovascular system of a user, the cardiovascular system including aheart and the user having a wrist covered by skin, the devicecomprising: an elongate band extending around the wrist andnon-invasively engaging the skin on the wrist of the user, wherein theelongate band is releasably coupleable to a second wrist-worn electronicdevice; at least one pulse transit time (PTT) or pressure sensor coupledto the elongate band and non-invasively engaging the skin over the wristof the user for measuring user signals from the cardiovascular system ofthe user; a controller coupled to the elongate band and at least one PTTor pressure sensor for determining relative or absolute blood pressuresignals based on the user signals; a power source coupled to theelongate band and the controller or the at least one PTT or pressuresensor; and a telemetry interface coupled to the elongate band and thecontroller.
 35. The device of claim 34, wherein the second wrist-wornelectronic device comprises a watch or heart rate monitor having ahousing encasing a second controller, second power source, and secondtelemetry interface, wherein the elongate band further comprises atleast one connection feature for securing the band to the watch or heartrate monitor.
 36. (canceled)
 37. The device of claim 34, wherein the atleast one PTT sensor comprises: a first sensor configured to measure afirst user signal indicative of ventricular ejection of blood from theheart of the user, the first sensed ventricular ejection signal havingan associated ventricular ejection time; and a second sensor configuredto measure a second user signal indicative of arrival of a pressurepulse in the wrist, the second sensed pressure pulse signal associatedwith the first sensed ventricular ejection and having an associatedpulse arrival time, wherein the relative blood pressure signal isdetermined from a difference between the ventricular ejection time andthe pulse arrival time.
 38. The device of claim 37, wherein the firstsensor comprises at least one impedance cardiogram (ICG),electrocardiogram (ECG), ballistocardiogram (BCG), phonocardiogram(PCG), or seismocardiogram (SCG) sensor coupled to the elongate band.39. The device of claim 38, wherein the at least one ICG or ECG sensorcomprises at least a first pair of dry electrodes configured tonon-invasively engage glabrous skin on an anterior surface of the wristand a second pair of dry electrodes configured to be contacted by atleast two fingers of an opposite hand.
 40. The device of claim 38,wherein the at least one ICG or ECG sensor comprises at least a firstpair of dry electrodes configured to non-invasively engage glabrous skinon an anterior surface of the wrist and a second pair of dry electrodesconfigured to non-invasively engage a sternum.
 41. The device of claim38, wherein the at least one BCG sensor comprises an accelerometerconfigured to non-invasively engage an anterior surface of the wrist soas to passively measure a relative blood pressure.
 42. The device ofclaim 38, wherein the at least one PCG sensor comprises a sound sensorconfigured to non-invasively engage a sternum.
 43. The device of claim38, wherein the at least SCG sensor comprises an accelerometerconfigured to non-invasively engage a sternum.
 44. The device of claim37, wherein the first sensor comprises first and second cardiogramsensors coupled to the elongate band for sensing the first user signalindicative of ventricular ejection of blood from the heart of the user,wherein the second cardiogram sensor is different than the firstcardiogram sensor, wherein the first and second cardiogram sensorscomprise an impedance cardiogram (ICG), electrocardiogram (ECG),ballistocardiouram (BCG), phonocardiogram (PCG), or seismocardiogram(SCG) sensor.
 45. (canceled)
 46. The device of claim 37, wherein thesecond sensor comprises at least one photoplethysmogram (PPG) sensor orphysical pressure pulse sensor coupled to the elongate band, wherein theat least one PPG sensor comprises at least one infra-red, red, or greenoptical source and a detector configured to be positioned over a radialartery of the wrist of the user, wherein the physical pressure pulsesensor comprises at least one pressure transducer, accelerometer, orstrain gauge configured to be positioned over a radial artery of thewrist of the user. 47.-48. (canceled)
 49. The device of claim 34,wherein the pressure sensor comprises at least one pressure transducer,piezoelectric film, or piezoresistive sensor configured tonon-invasively engage an anterior surface of the wrist of the user andbe positioned over a radial artery so as to passively or activelymeasure the absolute blood pressure signals, further comprising at leastone actuator coupled to the elongate band and configured to apply aconstant or variable pressure over a radial artery of the wrist. 50.(canceled)
 51. The device of claim 34, further comprising at least oneheight sensor, barometric pressure sensor, gyroscope, or accelerometercoupled to the elongate band so as to account for hydrostatic pressureeffects.
 52. The device of claim 34, wherein the telemetry interface ofthe elongate band is configured to transmit the relative or absoluteblood pressure signals to the second wrist-worn electronic device, amobile device, tablet, computer, or database.
 53. The device of claim34, wherein the telemetry interface of the elongate band is configuredto transmit the relative or absolute blood pressure signals to anelectronic health or medical record or health application software. 54.The device of claim 34, wherein the telemetry interface of the elongateband is configured to transmit the relative or absolute blood pressuresignals to a display on the second wrist-worn electronic device or athird non-wrist device, the display viewable by the user or a healthcare professional.
 55. The device of claim 34, wherein the telemetryinterface of the elongate band is configured to transmit trending datafor a time period based on the relative blood pressure signals, whereinthe time period comprises one or more days, weeks, months, or years.56.-68. (canceled)